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1.
Int J Pharm Compd ; 25(2): 163-168, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33798116

RESUMEN

An oral liquid formulation of nadolol, which is required for administration to patients who cannot swallow intact tablets, is not commercially available. The objective of this study was to evaluate the stability of nadolol 10 mg/mL prepared in Oral Mix vehicle and stored in amber glass, amber polyethylene terephthalate, or amber polyvinyl chloride for 91 days at 4ÆC and 25ÆC; and polypropylene oral plastic syringes at 25ÆC only. Three separate batches of nadolol suspension 10 mg/mL were prepared with Oral Mix. Of the suspension, 50-mL aliquots were stored in 100-mL bottles (amber glass, amber polyethylene terephthalate, or amber polyvinyl chloride). Half of the bottles from each container type were stored at 25ÆC and the other half at 4ÆC. On study days 0, 2, 7, 14, 21, 28, 42, 56, 72, and 91, nadolol concentration was determined using a reverse-phase, stability-indicating liquid chromatographic method from samples drawn from each type of container at each temperature. Oral syringes (3 mL), filled with 2 mL of suspension, were stored at 25ÆC and tested on days 0, 2, 7, 21, 42, and 91. The concentration of nadolol 10 mg/mL in Oral Mix in all study samples from bottles and oral syringes remained within 3.5% of the initial concentration. Based on the fastest degradation rate with 95% confidence, on day 91, between 99% to 100% and 98% to 100% remained in suspensions stored in bottles at 25ÆC and 4ÆC, respectively. Oral syringes at 25ÆC had 94% remaining on day 91. Multiple linear regression analysis demonstrated that the percent remaining was related to study day and container, but not temperature. On day 91, nadolol 10 mg/mL oral suspensions prepared with Oral Mix and stored in all bottle types at 4ÆC will retain more than 98% of the initial concentration compared to 99% at 25ÆC and only 94% when stored in oral syringes.


Asunto(s)
Nadolol , Jeringas , Administración Oral , Cromatografía Líquida de Alta Presión , Composición de Medicamentos , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Humanos , Plásticos , Suspensiones
2.
Int J Pharm Compd ; 25(2): 169-175, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33798117

RESUMEN

Metronidazole is indicated for the treatment of trichomoniasis, amebiasis, and anaerobic bacterial infections. The dosage regimen of metronidazole needs to be individualized in the treatment of trichomoniasis, in patients with hepatic impairment, and in pediatric as well as geriatric patients. A review of the therapeutic uses of metronidazole reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of metronidazole currently exists. Metronidazole is commercially available only as 250-mg and 500-mg film-coated tablets. An extemporaneously compounded suspension from pure drug powder or commercial tablets would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded metronidazole suspensions in PCCA SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two metronidazole concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating ultra-performance liquid chromatographic assay for the determination of the chemical stability of metronidazole in PCCA SuspendIt was developed and validated. Suspensions of metronidazole were prepared in PCCA SuspendIt at 25-mg/mL and 50-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5ÆC and 25ÆC). Samples were assayed initially and on the following time points (days): 7, 14, 28, 42, 59, 90, 122, and 180. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was also tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that metronidazole concentrations did not go below 97% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. Viscosity and pH values also did not change significantly. This study demonstrates that metronidazole is physically, chemically, and microbiologically stable in PCCA SuspendIt for 180 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for metronidazole in a liquid dosage form, with an extended beyond-use-date to meet patient needs.


Asunto(s)
Metronidazol , Administración Oral , Anciano , Niño , Cromatografía Líquida de Alta Presión , Cromonas , Composición de Medicamentos , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Humanos , Suspensiones
3.
Anticancer Res ; 41(4): 2111-2115, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813421

RESUMEN

BACKGROUND/AIM: It has been hypothesized that many, or even most cancers, utilize a unique immunomodulatory protein, called the progesterone induced blocking factor (PIBF) to allow spread of the cancer. Support for this concept has been provided by cancer cell line studies showing that PIBF is produced by these cancer cells and mifepristone suppresses this protein and inhibits proliferation of these cells. Furthermore, controlled murine studies with several spontaneous different types of cancer showed a clear beneficial effect of mifepristone over placebo control. Finally, there have been a variety of anecdotal reports showing efficacy of mifepristone in providing increased length and quality of life in patients with different types of advanced cancers. CASE REPORT: Single agent mifepristone was found to provide significant palliative benefit for a 51-year-old male whose metastatic advanced fibroblastic osteosarcoma progressed despite surgery, radiotherapy, multiagent chemotherapy, and targeted therapy. CONCLUSION: Thus, osteosarcoma can be added to the list of cancers, not necessarily associated with the classic nuclear progesterone receptor, that seem to respond to progesterone receptor antagonist therapy.


Asunto(s)
Neoplasias Óseas/tratamiento farmacológico , Mifepristona/administración & dosificación , Osteosarcoma/tratamiento farmacológico , Cuidados Paliativos/métodos , Administración Oral , Neoplasias Óseas/patología , Dolor en Cáncer/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Osteosarcoma/patología , Calidad de Vida , Tibia , Resultado del Tratamiento
4.
Sci Rep ; 11(1): 5087, 2021 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-33658615

RESUMEN

Non-steroidal anti-inflammatory drugs (NSAIDs) have been widely used in patients with respiratory infection, but their safety in coronavirus disease 19 (Covid-19) patients has not been fully investigated. We evaluated an association between NSAID use and outcomes of Covid-19. This study was a retrospective observational cohort study based on insurance benefit claims sent to the Health Insurance Review and Assessment Service of Korea by May 15, 2020. These claims comprised all Covid-19-tested cases and history of medical service use for the past 3 years in these patients. The primary outcome was all-cause mortality, and the secondary outcome was need for ventilator care. Among 7590 patients diagnosed with Covid-19, two distinct cohorts were generated based on NSAID or acetaminophen prescription within 2 weeks before Covid-19 diagnosis. A total of 398 patients was prescribed NSAIDs, and 2365 patients were prescribed acetaminophen. After propensity score matching, 397 pairs of data set were generated, and all-cause mortality of the NSAIDs group showed no significant difference compared with the acetaminophen group (4.0% vs. 3.0%; hazard ratio [HR], 1.33; 95% confidence interval [CI], 0.63-2.88; P = 0.46). The rate of ventilator care also did not show significantly different results between the two groups (2.0% vs. 1.3%; HR, 1.60; 95% CI 0.53-5.30; P = 0.42). Use of NSAIDs was not associated with mortality or ventilator care in Covid-19 patients. NSAIDs may be safely used to relieve symptoms in patients with suspicion of Covid-19.


Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , /mortalidad , Acetaminofén/efectos adversos , Acetaminofén/uso terapéutico , Administración Oral , Adulto , Anciano , Antiinflamatorios no Esteroideos/efectos adversos , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Puntaje de Propensión , República de Corea/epidemiología , Estudios Retrospectivos , /patogenicidad
5.
AAPS PharmSciTech ; 22(3): 108, 2021 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-33718989

RESUMEN

The combination of self-microemulsifying drug delivery system (SMEDDS) and mesoporous silica materials favors the oral delivery of poorly water-soluble drugs (PWSD). However, the influence of the surface property of the mesopores towards the drug release and in vivo pharmacokinetics is still unknown. In this study, SBA-15 with hydroxyl groups (SBA-15-H), methyl groups (SBA-15-M), amino groups (SBA-15-A), or carboxyl groups (SBA-15-C) was combined with SMEDDS containing sirolimus (SRL). The diffusion and self-emulsifying of SMEDDS greatly improved the drug release over the raw SRL and SRL-SBA-15-R (R referred to as the functional groups). Results of drug absorption and X-ray photoelectron spectroscopy (XPS) showed strong hydrogen binding between SRL and the amino groups of SBA-15-A, which hindered the drug release and oral bioavailability of SRL-SMEDDS-SBA-15-A. The favorable release of SRL-SMEDDS-SBA-15-C (91.31 ± 0.57%) and SRL-SMEDDS-SBA-15-M (91.76 ± 3.72%) contributed to enhancing the maximum blood concentration (Cmax) and the area under the concentration-time curve (AUC0→48). In conclusion, the release of SRL-SMEDDS-SBA-15-R was determined by the surface affinity of the SBA-15-R and the interaction between the SRL molecules and the surface of SBA-15-R. This study suggested that the SMEDDS-SBA-15 was a favorable carrier for PWSD, and the surface property of the mesopores should be considered for the optimization of the SMEDDS-SBA-15.


Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Liberación de Fármacos/fisiología , Absorción Intestinal/fisiología , Sirolimus/administración & dosificación , Sirolimus/farmacocinética , Administración Oral , Animales , Antibacterianos/administración & dosificación , Antibacterianos/química , Antibacterianos/farmacocinética , Disponibilidad Biológica , Perros , Emulsiones/administración & dosificación , Emulsiones/química , Emulsiones/farmacocinética , Absorción Intestinal/efectos de los fármacos , Masculino , Dióxido de Silicio/administración & dosificación , Dióxido de Silicio/química , Dióxido de Silicio/farmacocinética , Sirolimus/química , Solubilidad , Propiedades de Superficie
6.
FASEB J ; 35(4): e21360, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33749932

RESUMEN

The novel coronavirus disease, COVID-19, has grown into a global pandemic and a major public health threat since its breakout in December 2019. To date, no specific therapeutic drug or vaccine for treating COVID-19 and SARS has been FDA approved. Previous studies suggest that berberine, an isoquinoline alkaloid, has shown various biological activities that may help against COVID-19 and SARS, including antiviral, anti-allergy and inflammation, hepatoprotection against drug- and infection-induced liver injury, as well as reducing oxidative stress. In particular, berberine has a wide range of antiviral activities such as anti-influenza, anti-hepatitis C, anti-cytomegalovirus, and anti-alphavirus. As an ingredient recommended in guidelines issued by the China National Health Commission for COVID-19 to be combined with other therapy, berberine is a promising orally administered therapeutic candidate against SARS-CoV and SARS-CoV-2. The current study comprehensively evaluates the potential therapeutic mechanisms of berberine in preventing and treating COVID-19 and SARS using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analysis, and in silico molecular docking. An orally available immunotherapeutic-berberine nanomedicine, named NIT-X, has been developed by our group and has shown significantly increased oral bioavailability of berberine, increased IFN-γ production by CD8+ T cells, and inhibition of mast cell histamine release in vivo, suggesting a protective immune response. We further validated the inhibition of replication of SARS-CoV-2 in lung epithelial cells line in vitro (Calu3 cells) by berberine. Moreover, the expression of targets including ACE2, TMPRSS2, IL-1α, IL-8, IL-6, and CCL-2 in SARS-CoV-2 infected Calu3 cells were significantly suppressed by NIT-X. By supporting protective immunity while inhibiting pro-inflammatory cytokines; inhibiting viral infection and replication; inducing apoptosis; and protecting against tissue damage, berberine is a promising candidate in preventing and treating COVID-19 and SARS. Given the high oral bioavailability and safety of berberine nanomedicine, the current study may lead to the development of berberine as an orally, active therapeutic against COVID-19 and SARS.


Asunto(s)
Antivirales/farmacología , Berberina/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Modelos Biológicos , Virus del SRAS/metabolismo , Síndrome Respiratorio Agudo Grave , Administración Oral , /metabolismo , Línea Celular , Simulación por Computador , Humanos , Pandemias , Síndrome Respiratorio Agudo Grave/tratamiento farmacológico , Síndrome Respiratorio Agudo Grave/metabolismo
7.
Indian J Ophthalmol ; 69(4): 987-989, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33727474

RESUMEN

A 42-year-old male patient presented with profound impairment of vision in both eyes, just as he was recovering from COVID-19. A known diabetic and hypertensive, he suffered from COVID-19 pneumonia further complicated by ARDS, septicaemia and acute kidney injury. His vision on presentation was finger counting close to face bilaterally with multiple, yellowish lesions at the posterior pole. Based on the clinical findings and previous blood culture report, it was diagnosed as candida retinitis and treated with oral and intravitreal anti-fungals. The lesions were regressing at follow-up. This is a post COVID-19 presumed candida retinitis case report.


Asunto(s)
/diagnóstico , Candidiasis/diagnóstico , Infecciones Fúngicas del Ojo/diagnóstico , Infecciones Oportunistas/diagnóstico , Retinitis/diagnóstico , Administración Oral , Adulto , Antifúngicos/uso terapéutico , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Fluconazol/uso terapéutico , Humanos , Inyecciones Intravítreas , Masculino , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/microbiología , Retinitis/tratamiento farmacológico , Retinitis/microbiología , Tomografía de Coherencia Óptica , Agudeza Visual/fisiología , Voriconazol/uso terapéutico
8.
Rev Esp Quimioter ; 34(2): 81-92, 2021 Apr.
Artículo en Español | MEDLINE | ID: mdl-33749214

RESUMEN

From a microbiological point of view, both empirical and targeted antimicrobial treatment in respiratory infection is based on the sensitivity profile of isolated microorganisms and the possible resistance mechanisms that they may present. The latter may vary in different geographic areas according to prescription profiles and vaccination programs. Beta-lactam antibiotics, fluoroquinolones, and macrolides are the most commonly used antimicrobials during the exacerbations of chronic obstructive pulmonary disease and community-acquired pneumonia. In their prescription, different aspects such as intrinsic activity, bactericidal effect or their ability to prevent the development of resistance must be taken into account. The latter is related to the PK/PD parameters, the mutant prevention concentration and the so-called selection window. More recently, the potential ecological impact has grown in importance, not only on the intestinal microbiota, but also on the respiratory one. Maintaining the state of eubiosis requires the use of antimicrobials with a low profile of action on anaerobic bacteria. With their use, the resilience of the bacterial populations belonging to the microbiota, the state of resistance of colonization and the collateral damage related to the emergence of resistance to the antimicrobials in pathogens causing the infections and in the bacterial populations integrating the microbiota.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Administración Oral , Antibacterianos/administración & dosificación , Chlamydophila pneumoniae/efectos de los fármacos , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/microbiología , Progresión de la Enfermedad , Microbioma Gastrointestinal/efectos de los fármacos , Haemophilus influenzae/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Moraxella catarrhalis/efectos de los fármacos , Mycoplasma pneumoniae/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Infecciones del Sistema Respiratorio/microbiología , Staphylococcus aureus/efectos de los fármacos , Streptococcus pneumoniae/efectos de los fármacos
9.
Lancet Haematol ; 8(4): e289-e298, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33770484

RESUMEN

BACKGROUND: Primary immune thrombocytopenia is an autoimmune bleeding disorder. Preclinical reports suggest that the sialidase inhibitor oseltamivir induces a platelet response in the treatment of immune thrombocytopenia. This study investigated the activity and safety of dexamethasone plus oseltamivir versus dexamethasone alone as initial treatment in adult patients with primary immune thrombocytopenia. METHODS: This multicentre, randomised, open-label, parallel group, phase 2 trial was done in five tertiary medical hospitals in China. Eligible patients were aged 18 years or older with newly diagnosed, treatment-naive primary immune thrombocytopenia. Participants were randomly assigned (1:1), using block randomisation, to receive either dexamethasone (orally at 40 mg per day for 4 days) plus oseltamivir (orally at 75 mg twice a day for 10 days) or dexamethasone monotherapy (orally at 40 mg a day for 4 days). Patients who did not respond to treatment (platelet counts remained <30 × 109 cells per L or showed bleeding symptoms by day 10) were given an additional cycle of dexamethasone for 4 days in each group. Patients in the dexamethasone plus oseltamivir group who relapsed (platelet counts reduced again to <30 × 109 cells per L) after an initial response were allowed a supplemental course of oseltamivir (75 mg twice a day for 10 days). The coprimary endpoints were 14-day initial overall response and 6-month overall response. Complete response was defined as a platelet count at or above 100 × 109 cells per L and an absence of bleeding. Partial response was defined as a platelet count at or above 30 × 109 cells per L but less than 100 × 109 cells per L and at least a doubling of the baseline platelet count and an absence of bleeding. A response lasting for at least 6 months without any additional primary immune thrombocytopenia-specific intervention was defined as sustained response. All patients who were randomly assigned and received the allocated intervention were included in the modified intention-to-treat population analysis. This study has been completed and is registered with ClinicalTrials.gov, number NCT01965626. FINDINGS: From Feb 1, 2016, to May 1, 2019, 120 patients were screened for eligibility, of whom 24 were ineligible and excluded, 96 were enrolled and randomly assigned to receive dexamethasone plus oseltamivir (n=47) or dexamethasone (n=49), and 90 were included in the modified intention-to-treat analysis. Six patients did not receive the allocated intervention. Patients in the dexamethasone plus oseltamivir group had a significantly higher initial response rate (37 [86%] of 43 patients) than did those in the dexamethasone group (31 [66%] of 47 patients; odds ratio [OR] 3·18; 95 CI% 1·13-9·23; p=0·030) at day 14. The 6-month sustained response rate in the dexamethasone plus oseltamivir group was also significantly higher than that in the dexamethasone group (23 [53%] vs 14 [30%]; OR 2·17; 95 CI% 1·16-6·13; p=0·032). During the median follow-up of 8 months (IQR 5-14), two of 90 patients discontinued treatment due to serious adverse events (grade 3); one (2%) patient with general oedema in the dexamethasone plus oseltamivir group and one (2%) patient with fever in the dexamethasone group. The most frequently observed adverse events of any grade were fatigue (five [12%] of 43 in the dexamethasone plus oseltamivir group vs eight [17%] of 47 in the dexamethasone group), gastrointestinal reactions (eight [19%] vs three [6%]), insomnia (seven [16%] vs four [9%]), and anxiety (five [12%] vs three [6%]). There were no grade 4 or 5 adverse events and no treatment-related deaths. INTERPRETATION: Dexamethasone plus oseltamivir offers a readily available combination therapy in the management of newly diagnosed primary immune thrombocytopenia. The preliminary activity of this combination warrants further investigation. Multiple cycles of oseltamivir, as a modification of current first-line treatment, might be more effective in maintaining the platelet response. FUNDING: National Natural Science Foundation of China.


Asunto(s)
Dexametasona/uso terapéutico , Inhibidores Enzimáticos/uso terapéutico , Glucocorticoides/uso terapéutico , Oseltamivir/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Administración Oral , Adulto , China/epidemiología , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Inhibidores Enzimáticos/administración & dosificación , Inhibidores Enzimáticos/efectos adversos , Femenino , Estudios de Seguimiento , Glucocorticoides/administración & dosificación , Glucocorticoides/efectos adversos , Hemorragia/epidemiología , Humanos , Análisis de Intención de Tratar/métodos , Masculino , Persona de Mediana Edad , Oseltamivir/administración & dosificación , Oseltamivir/efectos adversos , Recuento de Plaquetas/estadística & datos numéricos , Recuento de Plaquetas/tendencias , Púrpura Trombocitopénica Idiopática/inmunología , Seguridad , Resultado del Tratamiento
10.
Medicine (Baltimore) ; 100(10): e25164, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33725918

RESUMEN

RATIONALE: Herein, we report 3 hemodialysis patients with idiopathic hypereosinophilic syndrome who were successfully treated using corticosteroid therapy. PATIENT CONCERNS: Case 1 was a 63-year-old man who was undergoing hemodialysis because of bilateral nephrectomy and developed hypereosinophilia with digestive symptoms, myocardial injury, and intradialytic hypotension. Case 2 was an 83-year-old man who was undergoing hemodialysis because of nephrosclerosis and developed hypereosinophilia with pruritus, myocardial injury, and intradialytic hypotension. Case 3 was a 59-year-old man who was undergoing hemodialysis because of diabetic nephropathy and developed hypereosinophilia with pruritus, myocardial injury, and intradialytic hypotension. DIAGNOSES: All 3 patients presented with hypereosinophilia (eosinophil count ≥1500 /µL for more than 1 month) and multiple-organ involvement (intradialytic hypotension, cardiac injury, digestive symptoms, and allergic dermatitis). A specific cause for the hypereosinophilia was not identified by systemic computed tomography, electrocardiography, echocardiography, bone marrow examination, or blood tests. Furthermore, Case 2 and 3 had not recently started taking any new drugs and drug-induced lymphocyte stimulation tests were negative in Case 1. Therefore, they were diagnosed with idiopathic hypereosinophilic syndrome. INTERVENTIONS: All 3 patients received corticosteroid therapy with prednisolone at a dose of 40 mg/d, 30 mg/d, and 60 mg/d in Case 1, 2, and 3, respectively. OUTCOMES: Their digestive symptoms, pruritus, intradialytic hypotension, and serum troponin I concentrations were immediately improved alongside reductions in their eosinophil counts. LESSONS: There have been few case reports of idiopathic hypereosinophilic syndrome in patients undergoing hemodialysis. We believe that recording of the clinical findings and treatments of such patients is mandatory to establish the optimal management of idiopathic hypereosinophilic syndrome.


Asunto(s)
Glucocorticoides/administración & dosificación , Síndrome Hipereosinofílico/tratamiento farmacológico , Diálisis Renal/efectos adversos , Insuficiencia Renal/terapia , Administración Oral , Anciano de 80 o más Años , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/terapia , Diagnóstico Diferencial , Relación Dosis-Respuesta a Droga , Eosinófilos , Humanos , Síndrome Hipereosinofílico/sangre , Síndrome Hipereosinofílico/diagnóstico , Síndrome Hipereosinofílico/etiología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Nefrectomía/efectos adversos , Nefroesclerosis/complicaciones , Nefroesclerosis/terapia , Prednisolona/administración & dosificación , Insuficiencia Renal/etiología , Resultado del Tratamiento
11.
Medicine (Baltimore) ; 100(12): e24522, 2021 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-33761634

RESUMEN

BACKGROUND: The intracranial hemorrhage (ICH) risk of oral anticoagulants/non-vitamin K antagonist oral anticoagulants (NOACs) remains largely unknown. Patients who need oral anticoagulants such as aspirin or warfarin often suffer from obvious complications. METHODS: This network meta-analysis intended to assess the ICH risk in patients taking NOACs. The data from PubMed, the Cochrane database, and Embase were reviewed. All phase III randomized controlled trials of NOACs (apixaban, edoxaban, dabigatran, rivaroxaban), aspirin and warfarin were reviewed. RESULTS: Twenty-three trials involving 137,713 participants were included, involving 6 regimens. Warfarin had the first risk of ICH (surface under the cumulative ranking area: 0.82), followed by dabigatran, edoxaban, aspirin, apixaban, rivaroxaban, and placebo. Dabigatran had the lowest risk of all-cause mortality (surface under the cumulative ranking area: 0.63), followed by apixaban, edoxaban, warfarin, rivaroxaban, aspirin, and placebo. CONCLUSION: Warfarin significantly increased the risk of ICH in patients taking oral anticoagulants compared with 4 NOACs (dabigatran, edoxaban, apixaban, rivaroxaban) and aspirin. Apixaban is least likely to induce all-cause mortality.


Asunto(s)
Antitrombinas/efectos adversos , Aspirina/efectos adversos , Hemorragias Intracraneales/epidemiología , Warfarina/efectos adversos , Administración Oral , Antitrombinas/administración & dosificación , Aspirina/administración & dosificación , Ensayos Clínicos Fase III como Asunto , Humanos , Hemorragias Intracraneales/inducido químicamente , Mortalidad , Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Medición de Riesgo/estadística & datos numéricos , Warfarina/administración & dosificación
12.
Zhongguo Zhong Yao Za Zhi ; 46(5): 1120-1127, 2021 Mar.
Artículo en Chino | MEDLINE | ID: mdl-33787105

RESUMEN

To evaluate the effects of Hydroxypropyl methylcellulose acetate succinate(HPMCAS MF) on absorption of silybin(SLB) from supersaturable self-nanoemulsifying drug delivery system which was pre-prepared at the early stage experiment. The cell toxicity of self-emulsifying preparation was evaluated by the MTT method, and the in vitro membrane permeability and absorption promoting effect of the self-emulsifying preparation were evaluated by establishing a Caco-2 cell monolayer model. The in vivo and in vitro supersaturation correlation was evaluated via the blood concentration of SLB. The results of MTT showed that the concentration of the preparation below 2 mg·mL~(-1)(C_(SLB) 100 µg·mL~(-1)) was not toxic to Caco-2 cells, and the addition of polymer had no significant effect on Caco-2 cells viability. As compared with the solution group, the transport results showed that the P_(app)(AP→BL) of the self-emulsifying preparation had a very significant increase; the transport rate of silybin can be reduced by polymer in 0-30 min; however, there was no difference in supersaturated transport between supersaturated SLB self-nanoemulsion drug delivery system(SLB-SSNEDDS) and SLB self-nanoemulsion drug delivery system(SLB-SNEDDS) within 2 hours. As compared with SLB suspension, pharmacokinetic parameters showed that the blood concentration of both SLB-SNEDDS and SLB-SSNEDDS groups were significantly increased, and C_(max) was 5.25 times and 9.69 times respectively of that in SLB suspension group, with a relative bioavailability of 578.45% and 1 139.44% respectively. C_(max) and relative bioavailability of SLB-SSNEDDS were 1.85 times and 197% of those of SLB-SNEDDS, respectively. Therefore, on the one hand, SSNEDDS can increase the solubility of SLB in gastrointestinal tract by maintaining stability of SLB supersaturation state; on the other hand, the osmotic transport process of SLB was regulated through the composition of its preparations, and both of them could jointly promote the transport and absorption of SLB to improve the oral bioavailability of SLB.


Asunto(s)
Sistemas de Liberación de Medicamentos , Nanopartículas , Administración Oral , Disponibilidad Biológica , Células CACO-2 , Emulsiones , Humanos , Metilcelulosa/análogos & derivados , Tamaño de la Partícula , Silibina , Solubilidad
13.
Medicine (Baltimore) ; 100(11): e25216, 2021 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-33726018

RESUMEN

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) have been widely used for stroke prevention in atrial fibrillation (AF) and the treatment and prevention of venous thromboembolism. There is an issue with safety, especially in clinically relevant bleeding. We performed a network meta-analysis to evaluate the risk of major gastrointestinal (GI) bleeding associated with NOACs. METHODS: Interventions were warfarin, enoxaparin, apixaban, dabigatran, edoxaban, and rivaroxaban. The primary outcome was the incidence of major GI bleeding. A subgroup analysis was performed according to the following indications: AF, deep venous thrombosis/pulmonary embolism, and postsurgical prophylaxis. RESULTS: A total of 29 randomized controlled trials (RCTs) and 4 large observation population studies were included. Compared with warfarin, apixaban showed a decreased the risk of major GI bleeding (relative risk [RR] 0.54, 95% confidence interval [CI] 0.25-0.76), and rivaroxaban tended to increase this risk (RR 1.40, 95% CI 1.06-1.85). Dabigatran (RR 1.25, 95% CI 0.98-1.60), edoxaban (RR 1.07, 95% CI 0.69-1.65), and enoxaparin (RR 1.24, 95% CI 0.63-2.43) did not significantly increase the risk of GI bleeding than did warfarin. In the subgroup analysis, according to indications, apixaban showed a decreased risk of major GI bleeding (RR 0.50, 95% CI 0.34-0.74) than did warfarin in AF studies. Dabigatran (RR 2.36, 95% CI 1.55-3.60, and rivaroxaban (RR 1.75, 95% CI 1.10-6.41) increased the risk of major GI bleeding than did apixaban. An analysis of studies on venous thromboembolism or pulmonary embolism showed that no individual NOAC or enoxaparin was associated with an increased risk of major GI bleeding compared to warfarin. CONCLUSION: Individual NOACs had varying profiles of GI bleeding risk. Results of analyses including only RCTs and those including both RCTs and population studies showed similar trends, but also showed several differences.


Asunto(s)
Anticoagulantes/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Hemorragia Gastrointestinal/inducido químicamente , Embolia Pulmonar/tratamiento farmacológico , Tromboembolia Venosa/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Fibrilación Atrial/complicaciones , Dabigatrán/efectos adversos , Enoxaparina/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metaanálisis en Red , Estudios Observacionales como Asunto , Embolia Pulmonar/complicaciones , Pirazoles/efectos adversos , Piridinas/efectos adversos , Piridonas/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Rivaroxabán/efectos adversos , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control , Tiazoles/efectos adversos , Tromboembolia Venosa/complicaciones , Warfarina/efectos adversos
14.
AAPS PharmSciTech ; 22(3): 92, 2021 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-33683477

RESUMEN

Venetoclax (VX) used in the treatment of chronic lymphocytic leukemia possesses low oral bioavailability (5.4%) and undergoes first-pass metabolism. Development of a formulation to overcome its bioavailability problem can be done by using nanocrystals which has many scientific applications. Nanocrystals of VX were formulated using amalgamation of precipitation and high-pressure homogenization method, in which polyvinyl alcohol (PVA) was selected as stabilizer. Process parameters like concentration of stabilizer, homogenization pressure, number of homogenization cycle, and concentration of lyoprotectant were optimized to obtain the desired particle size for the preparation of nanocrystal formulation. HPLC methods were developed and validated in-house for determination of in vitro dissolution data and in vivo bioavailability data. Physicochemical characterization was done to determine the particle size (zeta sizer), crystalline nature (DSC and XRPD), solubility (shaker bath), and dissolution (USP type 2 apparatus). Lyophilized VX nanocrystals of size less than 350 nm showed substantial increase in saturation solubility (~20 folds) and dissolution in comparison with free VX. In vitro release study revealed that 100% dissolution was achieved in 120 min as compared to VX free base which is having less than 43.5% dissolution in 120 min. Formulations of VX remain stable for 6 months under accelerated stability conditions. In vivo pharmacokinetic data in male Sprague-Dawley rats showed (~2.02 folds) significant increase in oral bioavailability of VX formulation as compared to free drug because of rapid dissolution and absorption which makes the nanocrystal formulation a better approach for oral administration of poorly soluble drugs.


Asunto(s)
Antineoplásicos/administración & dosificación , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Sulfonamidas/administración & dosificación , Administración Oral , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Disponibilidad Biológica , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacocinética , Cromatografía Líquida de Alta Presión , Liofilización , Masculino , Nanopartículas , Tamaño de la Partícula , Alcohol Polivinílico , Ratas , Ratas Sprague-Dawley , Solubilidad , Sulfonamidas/química , Sulfonamidas/farmacocinética
15.
Int J Nanomedicine ; 16: 1725-1741, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33688188

RESUMEN

Purpose: This study systematically investigated the potential of four model drugs (verapamil HCl, flurbiprofen, atenolol, and furosemide), each belonging to a different class of Biopharmaceutics Classification Systems (BCS) to be developed into oral modified release dosage forms after loading with halloysite nanotubes (HNTs). Methods: The drugs were studied for their loading (mass gain %) by varying solvent system, method, pH, and ratios of loading into the nanotubes using D-optimal split-plot design with the help of Design Expert software. Drug-loaded halloysites were characterized by XRD, DTA, FTIR, SEM, and HPLC-UV-based assay procedures. Dissolution studies were also performed in dissolution media with pH 1.2, 4.5, and 6.8. Moreover, the optimized samples were evaluated under stress stability conditions for determining prospects for the development of oral dosage forms. Results: As confirmed with the results of XRD and DTA, the drugs were found to be converted into amorphous form after loading with halloysite (HNTs). The drugs were loaded in the range of ~7-9% for the four drugs, with agitation providing satisfactory and equivalent loading as compared to vacuum plus agitation based reported methods. FTIR results revealed either only weak electrostatic (verapamil HCl and flurbiprofen) or no interaction with the surface structure of the HNTs. The dissolution profiling depicted significantly retarded release of drugs with Fickian diffusion from a polydisperse system as a model that suits well for the development of oral dosage forms. HPLC-UV-based assay indicated that except furosemide (BCS class IV), the other three drugs are quite suitable for development for oral dosage forms. Conclusion: The four drugs investigated undergo phase transformation with HNTs. While agitation is an optimum method for loading drugs with various physicochemical attributes into HNTs; solvent system, loading ratios and pH play an important role in the loading efficiency respective to the drug properties. The study supports the capability of developing HNT-based modified release oral dosage forms for drugs with high solubility.


Asunto(s)
Biofarmacia/clasificación , Arcilla/química , Sistemas de Liberación de Medicamentos , Liberación de Fármacos , Nanotubos/química , Preparaciones Farmacéuticas/administración & dosificación , Administración Oral , Silicatos de Aluminio/química , Cinética , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X
16.
N Engl J Med ; 384(12): 1101-1112, 2021 03 25.
Artículo en Inglés | MEDLINE | ID: mdl-33761207

RESUMEN

BACKGROUND: The oral Janus kinase 1 (JAK1) inhibitor abrocitinib, which reduces interleukin-4 and interleukin-13 signaling, is being investigated for the treatment of atopic dermatitis. Data from trials comparing JAK1 inhibitors with monoclonal antibodies, such as dupilumab, that block interleukin-4 receptors are limited. METHODS: In a phase 3, double-blind trial, we randomly assigned patients with atopic dermatitis that was unresponsive to topical agents or that warranted systemic therapy (in a 2:2:2:1 ratio) to receive 200 mg or 100 mg of abrocitinib orally once daily, 300 mg of dupilumab subcutaneously every other week (after a loading dose of 600 mg), or placebo; all the patients received topical therapy. The primary end points were an Investigator's Global Assessment (IGA) response (defined as a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4], with an improvement of ≥2 points from baseline) and an Eczema Area and Severity Index-75 (EASI-75) response (defined as ≥75% improvement from baseline in the score on the EASI [scores range from 0 to 72]) at week 12. The key secondary end points were itch response (defined as an improvement of ≥4 points in the score on the Peak Pruritus Numerical Rating Scale [scores range from 0 to 10]) at week 2 and IGA and EASI-75 responses at week 16. RESULTS: A total of 838 patients underwent randomization; 226 patients were assigned to the 200-mg abrocitinib group, 238 to the 100-mg abrocitinib group, 243 to the dupilumab group, and 131 to the placebo group. An IGA response at week 12 was observed in 48.4% of patients in the 200-mg abrocitinib group, 36.6% in the 100-mg abrocitinib group, 36.5% in the dupilumab group, and 14.0% in the placebo group (P<0.001 for both abrocitinib doses vs. placebo); an EASI-75 response at week 12 was observed in 70.3%, 58.7%, 58.1%, and 27.1%, respectively (P<0.001 for both abrocitinib doses vs. placebo). The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. Nausea occurred in 11.1% of the patients in the 200-mg abrocitinib group and 4.2% of those in the 100-mg abrocitinib group, and acne occurred in 6.6% and 2.9%, respectively. CONCLUSIONS: In this trial, abrocitinib at a dose of either 200 mg or 100 mg once daily resulted in significantly greater reductions in signs and symptoms of moderate-to-severe atopic dermatitis than placebo at weeks 12 and 16. The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. (Funded by Pfizer; JADE COMPARE ClinicalTrials.gov number, NCT03720470.).


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Dermatitis Atópica/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirimidinas/administración & dosificación , Sulfonamidas/administración & dosificación , Administración Oral , Adulto , Anticuerpos Monoclonales Humanizados/efectos adversos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Humanos , Inmunoglobulina A/sangre , Inyecciones Subcutáneas , Subunidad alfa del Receptor de Interleucina-4/antagonistas & inhibidores , Janus Quinasa 1/antagonistas & inhibidores , Masculino , Placebos/uso terapéutico , Inhibidores de Proteínas Quinasas/efectos adversos , Prurito/tratamiento farmacológico , Pirimidinas/efectos adversos , Índice de Severidad de la Enfermedad , Sulfonamidas/efectos adversos
17.
Environ Health Prev Med ; 26(1): 38, 2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33752586

RESUMEN

BACKGROUND: Periploca aphylla is used by local population and indigenous medicine practitioners as stomachic, tonic, antitumor, antiulcer, and for treatment of inflammatory disorders. The aim of this study was to evaluate antidiabetic effect of the extract of P. aphylla and to investigate antioxidant and hypolipidemic activity in streptozotocin (STZ)-induced diabetic rats. METHODS: The present research was conducted to evaluate the antihyperglycemic potential of methanol extract of P. aphylla (PAM) and subfractions n-hexane (PAH), chloroform (PAC), ethyl acetate (PAE), n-butanol (PAB), and aqueous (PAA) in glucose-overloaded hyperglycemic Sprague-Dawley rats. Based on the efficacy, PAB (200 mg/kg and 400 mg/kg) was tested for its antidiabetic activity in STZ-induced diabetic rats. Diabetes was induced via intraperitoneal injection of STZ (55 mg/kg) in rat. Blood glucose values were taken weekly. HPLC-DAD analysis of PAB was carried out for the presence of various polyphenols. RESULTS: HPLC-DAD analysis of PAB recorded the presence of rutin, catechin, caffeic acid, and myricetin. Oral administration of PAB at doses of 200 and 400 mg/kg for 21 days significantly restored (P < 0.01) body weight (%) and relative liver and relative kidney weight of diabetic rats. Diabetic control rats showed significant elevation (P < 0.01) of AST, ALT, ALP, LDH, total cholesterol, triglycerides, LDL, creatinine, total bilirubin, and BUN while reduced (P < 0.01) level of glucose, total protein, albumin, insulin, and HDL in serum. Count of blood cells and hematological parameters were altered in diabetic rats. Further, glutathione peroxidase, catalase, superoxide dismutase, glutathione reductase, and total soluble protein concentration decreased while concentration of thiobarbituric acid reactive substances and percent DNA damages increased (P < 0.01) in liver and renal tissues of diabetic rats. Histopathological damage scores increased in liver and kidney tissues of diabetic rats. Intake of PAB (400 mg/kg) resulted in significant improvement (P < 0.01) of above parameters, and results were comparable to that of standard drug glibenclamide. CONCLUSION: The result suggests the antihyperglycemic, antioxidant, and anti-inflammatory activities of PAB treatment in STZ-compelled diabetic rat. PAB might be used as new therapeutic agent in diabetic patients to manage diabetes and decrease the complications.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Periploca/química , Fitoquímicos/administración & dosificación , Extractos Vegetales/administración & dosificación , 1-Butanol/química , Administración Oral , Animales , Diabetes Mellitus Experimental/inducido químicamente , Relación Dosis-Respuesta a Droga , Hipoglucemiantes/química , Masculino , Fitoquímicos/química , Extractos Vegetales/química , Ratas , Ratas Sprague-Dawley , Estreptozocina/efectos adversos
18.
BMC Pulm Med ; 21(1): 102, 2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-33761886

RESUMEN

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a pandemic affecting all countries in the world. Italy has been particularly afflicted by the health emergency, and since the peak phase has passed, major concern regarding medium to long term complications due to COVID-19 is arising. Little is known in literature regarding thromboembolic complications once healed after COVID-19. CASE PRESENTATION: A 51-year-old patient recovered from COVID-19 pneumonia complicated by pulmonary embolism (PE) came to the hospital for palpitations and chest pain. Although he was on treatment dose of direct oral anticoagulation (DOAC), massive recurrent PE was diagnosed. CONCLUSION: In the early post COVID-19 era, the question remains regarding the efficacy of DOACs in COVID-19 patients.


Asunto(s)
Anticoagulantes/administración & dosificación , Dabigatrán/administración & dosificación , Heparina/administración & dosificación , Embolia Pulmonar/prevención & control , Embolia Pulmonar/virología , Warfarina/administración & dosificación , Administración Oral , Anticoagulantes/uso terapéutico , Dabigatrán/uso terapéutico , Quimioterapia Combinada , Heparina/uso terapéutico , Humanos , Masculino , Persona de Mediana Edad , Embolia Pulmonar/tratamiento farmacológico , Recurrencia , Warfarina/uso terapéutico
19.
BMC Infect Dis ; 21(1): 285, 2021 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-33743592

RESUMEN

BACKGROUND: The systemic response to an infection might influence the pharmacokinetics of antibiotics. To evaluate the desired possibility of an earlier (< 24 h) IV-to-oral switch therapy in febrile non-ICU, hospitalized patients, a systematic review was performed to assess the effect of the initial phase of a systemic infection on the bioavailability of orally administered antibiotics in such patients. METHODS: An electronic search was conducted in MEDLINE and Embase up to July 2020. Studies were selected when outcome data were collected during the initial stage of a febrile disease. Outcome data were (maximum) serum concentrations, time of achieving maximum serum concentration, and the area-under-the-plasma-concentration-time curve or bioavailability of orally administered antibiotics. Risk of bias was assessed. RESULTS: We identified 9 studies on 6 antibiotics. Ciprofloxacin was the most frequently studied drug. Outcomes of the studies were heterogeneous and generally had a high risk of bias. Three small studies, two on ciprofloxacin and one on clarithromycin, compared the pharmacokinetics of febrile patients with those of clinically recovered patients and suggested that bioavailability was not altered in these patients. Other studies either compared the pharmacokinetics in febrile patients with reported pharmacokinetic values from earlier studies in healthy volunteers (n = 2), or provided no comparison at all and were non-conclusive (n = 4). CONCLUSION: There is a clear knowledge gap regarding the bioavailability of orally administered antibiotics in non-ICU patients during the initial phase of a systemic infection. Well-designed studies on this topic are necessary to elucidate whether patients can benefit from the advantages of an earlier IV-to-oral switch.


Asunto(s)
Antibacterianos/farmacocinética , Infecciones/tratamiento farmacológico , Administración Oral , Antibacterianos/uso terapéutico , Disponibilidad Biológica , Ciprofloxacino , Fiebre , Humanos
20.
Int J Nanomedicine ; 16: 2013-2044, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33727812

RESUMEN

Background: Sulpiride (SUL), is a selective antidopaminergic drug that had extensive biological activities. However, its sparingly aqueous solubility and limited gastrointestinal permeability lead to scanty oral bioavailability which hinders its clinical efficacy. Objective: SUL-loaded lipospheres (SUL-LPS) were designed to serve as an oral biocompatible nanovector for improving SUL permeability as well as conquering its low oral absorption and then in turn enhancing its antidepressant action. Methods: SUL-LPS were fabricated via two processing techniques namely, melt emulsification and solvent evaporation. The impact of different lipid cores, phospholipid shells together with various surfactant concentrations and types on the lipospheres properties were screened. Detailed physicochemical elucidations were performed followed by ex vivo permeation appraisal using the non-everted intestine model. The pharmacokinetic parameters of SUL-LPS, free SUL and marketed product were assessed following oral administration to healthy rats. Reserpine-induced depression rat model was used to assess the antidepressant action of SUL-LPS on which full behavioural and biochemical analysis was conducted. Safety attributes of nanoencapsulated SUL on the brain and other internal organs were evaluated. Results: The optimum LPS revealed an excellent nanosize with a narrow PdI, negative zeta potential and acceptable entrapment efficiency of 68.62 nm, 0.242, -30.4 mV and 84.12%, respectively. SUL-LPS showed a sustained release pattern and 2.1-fold enhancement in the intestinal permeation parameters with low mucin interaction. Oral pharmacokinetic appraisal exhibited that LPS provided 3.4-fold improvement in SUL oral bioavailability together with long-circulating properties, relative to the free drug. Pharmacodynamic study confirmed the superior antidepressant action of SUL-LPS as evident by 1.6 and 1.25-fold elevation in the serotonin and dopamine expressions, respectively. Meanwhile, nanotoxicological appraisal proved the biocompatibility of SUL-LPS upon repetitive oral administration. Conclusion: Rationally designed lipospheres hold promising in vitro and in vivo characteristics for efficient delivery of SUL with high oral bioavailability, antidepressant activity together with a good safety profile.


Asunto(s)
Antidepresivos/farmacología , Lípidos/química , Nanopartículas/química , Sulpirida/administración & dosificación , Sulpirida/farmacología , Administración Oral , Animales , Materiales Biocompatibles/química , Disponibilidad Biológica , Cromatografía Líquida de Alta Presión , Composición de Medicamentos , Liberación de Fármacos , Liofilización , Masculino , Mucinas/química , Nanopartículas/ultraestructura , Neurotransmisores/metabolismo , Especificidad de Órganos/efectos de los fármacos , Tamaño de la Partícula , Permeabilidad , Ratas Sprague-Dawley , Ratas Wistar , Sulpirida/química , Sulpirida/farmacocinética , Porcinos
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