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OBJECTIVES: To analyze the factors affecting the concentrations of the active moiety of risperidone (RIS) and its active metabolite 9-hydroxyrisperidone (9-OH-RIS) in psychiatric outpatients taking immediate-release formulations. METHODS: This is a retrospective study on the therapeutic drug monitoring (TDM) data regarding RIS and 9-OH-RIS in adult psychiatric outpatients. TDM data with simultaneous RIS and 9-OH-RIS monitoring from March 2018 to February 2020 and relevant medical records (including dosage, dosage form, sex, age, diagnosis, combined medication, and comorbid disease) from 399 adult psychiatric outpatients (223 males and 176 females) were included in this study. RESULTS: The daily dose of RIS was 5.56 ± 2.05 mg, the concentration of total active moiety was 42.35 ± 25.46 ng/mL, and the dose-adjusted plasma concentration (C/D) of active moiety was 7.83 ± 3.87 (ng/ml)/(mg/day). Dose, sex, and age were identified as important factors influencing concentrations of RIS and 9-OH-RIS in adult psychiatric outpatients. CONCLUSIONS: Individualized medication adjustments should be made according to the specific conditions of psychiatric outpatients. The findings strongly support the use of TDM to guide dosing decisions in psychiatric outpatients taking RIS.
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Antipsicóticos , Risperidona , Adulto , Masculino , Feminino , Humanos , Risperidona/uso terapêutico , Palmitato de Paliperidona/efeitos adversos , Antipsicóticos/efeitos adversos , Estudos Retrospectivos , Pacientes AmbulatoriaisRESUMO
PURPOSE: Anesthesia nurses play an important postsurgical role during the anesthesia recovery period, which is characterized by a high incidence of complications related to anesthesia and surgery. Strengthening staff allocation and skill management in the postanesthesia care unit (PACU) is therefore particularly important in managing length of stay. We aimed to investigate the effect of two schedule modes for anesthesia nurses on PACU efficiency. DESIGN: A retrospective observational cohort study. METHODS: We conducted a retrospective study in a large tertiary academic medical center. In 2018, the PACU operated with traditional scheduling and the nurse-to-patient ratio was 1.2:1. The PACU implemented intensive scheduling and this ratio was adjusted to 1:1 in 2019 by adjusting the anesthesia nurse allocation scheme. We compared the number of admitted patients, length of PACU stay, the incidence of anesthesia-related complications, and nurse satisfaction with the two modes. FINDINGS: The total number of admitted patients was 10,531 in 2018 and 10,914 in 2019. PACU admitted 401 more patients in 2019 than in 2018, even with two fewer nurses per day. Nevertheless, the median length of PACU stay in 2019 was statistically significantly shorter than in 2018 (29 [22-40] vs 28 [21-39], P < .001], while the incidence of anesthesia-related complications including postoperative pain, nausea and vomiting, hypertension, and shivering were comparable in the 2 years (P > .091). The intensive scheduling implemented in 2019 received more satisfaction from nurses than the traditional scheduling applied in 2018 (P < .01). CONCLUSIONS: The scheduling of anesthesia nurses affects PACU efficiency. The intensive scheduling mode implemented in 2019 resulted in a comparable number of admitted patients, a better quality of care, and higher nurse satisfaction than those under the traditional scheduling mode.
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Oral health is crucial to daily life, yet many people worldwide suffer from oral diseases. With the development of oral tissue engineering, there is a growing demand for dental biomaterials. Addressing oral diseases often requires a two-fold approach: fighting bacterial infections and promoting tissue growth. Hydrogels are promising tissue engineering biomaterials that show great potential for oral tissue regeneration and drug delivery. In this review, we present a classification of hydrogels commonly used in dental research, including natural and synthetic hydrogels. Furthermore, recent applications of these hydrogels in endodontic restorations, periodontal tissues, mandibular and oral soft tissue restorations, and related clinical studies are also discussed, including various antimicrobial and tissue growth promotion strategies used in the dental applications of hydrogels. While hydrogels have been increasingly studied in oral tissue engineering, there are still some challenges that need to be addressed for satisfactory clinical outcomes. This paper summarizes the current issues in the abovementioned application areas and discusses possible future developments.
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Hidrogéis , Engenharia Tecidual , Humanos , Materiais Biocompatíveis/farmacologia , Hidrogéis/farmacologia , PeriodontoRESUMO
Diabetic foot ulcers (DFU) are a vascular complication of diabetes mellitus (DM). It has been confirmed that irisin is closely related to DM. However, the effect of irisin on DFU is obscure and needs further study. After human umbilical vein endothelial cell lines (HUVECs) were treated with different concentrations' irisin, normal glucose, high glucose (HG), HG plus irisin-high (H) or sh-Notch1, cell biological behaviors, LDH, and VEGFA were detected by cell function experiments. Apoptosis- and Notch pathway-related protein levels were evaluated by Western blot. Irisin has no cytotoxicity, and irisin-H elevated cell viability and inhibited apoptosis and LDH level in HG-induced HUVECs. Meanwhile, irisin-H restored HG-repressed migration and angiogenesis in HUVECs. Irisin-H inhibited apoptosis-related protein levels and promoted VEGFA and Notch pathway-related protein levels in HG-treated HUVECs. Additionally, sh-Notch1 reversed the protective effect of irisin-H in HG-treated HUVECs. Irisin restores HG-induced cell injury and angiogenesis in HUVECs by activating Notch pathway via Notch1.
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Células Endoteliais da Veia Umbilical Humana , Apoptose , Sobrevivência Celular , Humanos , Proteínas Proto-Oncogênicas c-aktRESUMO
BACKGROUND: The objective of this study was to investigate the serum concentrations of olanzapine in relation to age, sex, and other factors in Chinese patients aged between 10 and 90 years. METHODS: Data for 884 olanzapine patients, deposited between 2016 and 2017, were retrieved from the therapeutic drug monitoring database of the Affiliated Brain Hospital of Guangzhou Medical University. The effects of covariates on serum olanzapine concentration, dose-normalized concentration (C/D ratio), and normalized concentration (C/D/weight) were investigated. RESULTS: Generally, male patients had lower olanzapine concentration, C/D ratio, and C/D/weight than female patients (P < 0.001). Smoking and drinking reduced olanzapine concentration, C/D ratio, and C/D/weight (P < 0.001). Coadministration with valproate decreased olanzapine concentration, C/D ratio, and C/D/weight by about 16%, 30%, and 40%, respectively (P < 0.001). Patients younger than 60 years had higher olanzapine concentrations (P < 0.05) but lower C/D ratios and C/D/weight (P < 0.001) than patients older than 60 years. Age was correlated with olanzapine concentration (r = -0.082, P < 0.05), C/D ratio (r = 0.196, P < 0.001), and C/D/weight (r = 0.169, P < 0.001). Sample timing after dose and diagnostic factors also contributed to the olanzapine concentrations. Multiple linear regression analysis revealed significant influences of dosage, age, sex, valproate comedication, smoking, postdose interval, and schizophrenia (vs bipolar affective disorders) on serum olanzapine concentrations. CONCLUSIONS: The metabolism of olanzapine may be altered by several factors. Patients characterized with a combination of factors may benefit from therapeutic drug monitoring for the adjustment of olanzapine dose to minimize adverse reactions.
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Antipsicóticos/sangue , Olanzapina/sangue , Adolescente , Adulto , Antipsicóticos/uso terapêutico , Povo Asiático , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olanzapina/uso terapêutico , Estudos Retrospectivos , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Fatores Sexuais , Fumar/sangue , Ácido Valproico/sangue , Ácido Valproico/uso terapêutico , Adulto JovemRESUMO
PURPOSE: This study aimed to investigate the influence of diagnosis, body weight, sex, age, smoking, formulations, and concomitant drugs on steady-state dose-corrected serum concentrations (C/D) of venlafaxine (VEN) and O-desmethylvenlafaxine (ODV). METHODS: A retrospective analysis of therapeutic drug monitoring (TDM) was carried out. Patients' demographic data, therapeutic regimens, and concentrations were collected. RESULTS: We included 91 verified samples from 80 patients. Females had by average 13% smaller body weight, 50% higher C/D of VEN, and VEN + ODV and 25% smaller ODV/VEN than males. Patients >60 years had by average 33-59% higher C/D levels of ODV and VEN + ODV than younger patients. The concomitant use of valproic acid caused an average 51% higher C/D of ODV and a 2.2-fold larger ODV/VEN, while clozapine was related with 40% smaller ratio of ODV/VEN and 38% lower C/D levels of ODV. Positive correlations were detected between valproic acid concentrations and the C/D of VEN and VEN + ODV. In a multiple linear regression analysis, variance in the C/D of VEN + ODV was partly attributed to the daily dose of VEN, sex, age and valproic acid concentration. CONCLUSION: Our results suggested daily dose of VEN, sex, age, and valproic acid as indicators for the C/D of VEN + ODV in Chinese patients. TDM as a valuable tool was suggested in elderly female patients and patients receiving polypharmacy.
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Succinato de Desvenlafaxina/farmacocinética , Ácido Valproico/farmacologia , Cloridrato de Venlafaxina/farmacocinética , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Povo Asiático , Clozapina/farmacologia , Succinato de Desvenlafaxina/sangue , Interações Medicamentosas , Monitoramento de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimedicação , Estudos Retrospectivos , Fatores Sexuais , Cloridrato de Venlafaxina/sangue , Adulto JovemRESUMO
Overexpression of gonadotropin-releasing hormone (GnRH) receptor in many tumors but not in normal tissues makes it possible to use GnRH analogs as targeting peptides for selective delivery of cytotoxic agents, which may help to enhance the uptake of anticancer drugs by cancer cells and reduce toxicity to normal cells. The GnRH analogs [d-Cys6 , desGly10 , Pro9 -NH2 ]-GnRH, [d-Cys6 , desGly10 , Pro9 -NHEt]-GnRH, and [d-Cys6 , α-aza-Gly10 -NH2 ]-GnRH were conjugated with doxorubicin (Dox), respectively, through N-succinimidyl-3-maleimidopropionate as a linker to afford three new GnRH-Dox conjugates. The metabolic stability of these conjugates in human serum was determined by RP-HPLC. The antiproliferative activity of the conjugates was examined in GnRH receptor-positive MCF-7 human breast cancer cell line by MTT assay. The three GnRH-Dox conjugates showed improved metabolic stability in human serum in comparison with AN-152. The antiproliferative effect of conjugate II ([d-Cys6 , desGly10 , Pro9 -NHEt]-GnRH-Dox) on MCF-7 cells was higher than that of conjugate I ([d-Cys6 , desGly10 , Pro9 -NH2 ]-GnRH-Dox) and conjugate III ([d-Cys6 , α-aza-Gly10 -NH2 ]-GnRH-Dox), and the cytotoxicity of conjugate II against GnRH receptor-negative 3T3 mouse embryo fibroblast cells was decreased in comparison with free Dox. GnRH receptor inhibition test suggested that the antiproliferative activity of conjugate II might be due to the cellular uptake mediated by the targeting binding of [d-Cys6 -des-Gly10 -Pro9 -NHEt]-GnRH to GnRH receptors. Our study indicates that targeting delivery of conjugate II mediated by [d-Cys6 -des-Gly10 -Pro9 -NHEt]-GnRH is a promising strategy for chemotherapy of tumors that overexpress GnRH receptors.
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Antibióticos Antineoplásicos/farmacologia , Citotoxinas/farmacologia , Doxorrubicina/farmacologia , Portadores de Fármacos , Hormônio Liberador de Gonadotropina/farmacologia , Oligopeptídeos/farmacologia , Animais , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Reagentes de Ligações Cruzadas/química , Citotoxinas/química , Citotoxinas/metabolismo , Doxorrubicina/análogos & derivados , Doxorrubicina/metabolismo , Estabilidade de Medicamentos , Expressão Gênica , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/síntese química , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Células MCF-7 , Maleimidas/química , Camundongos , Células NIH 3T3 , Oligopeptídeos/síntese química , Oligopeptídeos/metabolismo , Ligação Proteica , Receptores LHRH/genética , Receptores LHRH/metabolismo , Succinimidas/químicaRESUMO
PURPOSE/BACKGROUND: Blonanserin is a novel antipsychotic drug approved for the treatment of schizophrenia in East Asia. The main objective of the present study was to investigate the effect of alcohol on the pharmacokinetic properties of blonanserin and its metabolite N-deethyl blonanserin in healthy Chinese male subjects under fasting conditions. METHODS/PROCEDURES: The study was designed as a randomized, open-label, crossover clinical investigation in 10 male volunteers, each of whom received 2 treatments under fasted conditions: treatment A, blonanserin (8 mg) with water, and treatment B, blonanserin (8 mg) with alcohol (1 mL/kg). FINDINGS/RESULTS: The average values of areas under the curve (AUCs) and mean peak plasma concentrations (Cmax) were noticeably increased by alcohol consumption. In treatment A, average values of AUC0-24h, AUC0-∞, and Cmax were 3178 ng/h/L, 3879 ng/h/L, and 492 ng/L for blonanserin, and 1932 ng/h/L, 4208 ng/h/L, and 137 ng/L for N-deethylated blonanserin, respectively. In treatment B, AUC0-∞ and Cmax were both increased 2.4-fold for blonanserin and 1.4-fold and 1.7-fold, respectively, for N-deethylated blonanserin (P < 0.05). Compared with treatment A, clearance (Clz/F) of blonanserin and N-deethylated blonanserin decreased significantly (2.4-fold and 1.7-fold, respectively) in treatment B (P < 0.05). Alcohol delayed the absorption and reduced the clearance of blonanserin, leading to a 1.8-fold increase in the time to reach Cmax (Tmax) and half life time (t1/2) (P < 0.05). IMPLICATIONS/CONCLUSIONS: Alcohol increased the bioavailability of blonanserin and N-deethyl blonanserin in healthy subjects and the marked effect of alcohol on blonanserin bioavailability should be taken into consideration in deciding dosing schedules in clinical therapy.
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Antipsicóticos/farmacocinética , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Piperazinas/farmacocinética , Piperidinas/farmacocinética , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/sangue , Depressores do Sistema Nervoso Central/administração & dosagem , China , Estudos Cross-Over , Interações Medicamentosas , Etanol/administração & dosagem , Jejum , Humanos , Masculino , Piperazinas/administração & dosagem , Piperazinas/sangue , Piperidinas/administração & dosagem , Piperidinas/sangue , Adulto JovemRESUMO
1. A new oral liquid formulation combining guaifenesin, pseudoephedrine and hydrocodone is effective in improving the symptoms of common cold. The pharmacokinetic properties of the individual components were evaluated in a randomized, open-label, four-period study in 12 healthy Chinese volunteers following single and multiple doses. The data were compared with data for the individual ingredients in Antuss®. 2. In the single-dose period, exposure levels (AUC and Cmax) for guaifenesin, pseudoephedrine and hydrocodone increased directly as the dose of the oral liquid formulation increased from 5 to 15 mL. Only minor amounts of guaifenesin and hydrocodone were excreted in urine (â¼0.10% and 4.66%, respectively). Pseudoephedrine was mainly excreted unchanged, with 44.95% of the dose excreted in urine within 24 h. After multiple dosing, there was no obvious accumulation of any drug, as assessed by AUC. When considering Cmax, there was a trend toward accumulation of hydrocodone and pseudoephedrine. The pharmacokinetic profiles of guaifenesin and pseudoephedrine in the oral liquid formulation were similar to those in the branded preparation, Antuss®. 3. The newly developed oral liquid formulation combining guaifenesin, pseudoephedrine and hydrocodone was safe and well tolerated and might provide a reliable alternative to the branded formulation for patients with common colds.
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Guaifenesina/farmacocinética , Hidrocodona/farmacocinética , Pseudoefedrina/farmacocinética , Administração Oral , Adulto , Disponibilidade Biológica , Feminino , Voluntários Saudáveis , Humanos , MasculinoRESUMO
1. Ingestion of grapefruit juice and food could be factors affecting the pharmacokinetics of pirfenidone, a promising drug for treatment of idiopathic pulmonary fibrosis. 2. A randomized, open-label, three-period crossover study was carried out in 12 healthy Chinese male volunteers who were randomized to one of the three treatments: pirfenidone tablets (0.4 g) were orally administered to fasted or fed subjects, or with grapefruit juice. The washout period was 7 d. 3. Significantly reduced maximum plasma concentration (Cmax, 5.0 5 ± 1.39 versus 10.9 0 ± 2.94 mg·L(- 1)), modestly affected area-under-the-plasma concentration-time curve (AUC) from time zero to 12 h post dosing (AUC0-12 h, 21.8 9 ± 6.47 versus 26.1 6 ± 7.32 mg·h·L(- 1)) and delayed time to reach Cmax (Tmax) were observed in fed group compared with fasted group. Similar effects on Cmax (5.8 2 ± 1.23 versus 10.9 0 ± 2.94 mg·L(- 1)) and AUC0-12 h (modest but not statistically significant, 24.4 4 ± 7.40 versus 26.1 6 ± 7.32 mg·h·L(- 1)) were observed for grapefruit juice compared to fasted subjects. 4. Co-administration of pirfenidone with grapefruit juice resulted in modestly reduced overall oral absorption and significantly reduced peak concentrations compared to fasting, which was similar to effect of food ingestion. No adverse events were observed in the study, but relatively dramatic reduction of peak concentrations should raise concerns for clinical efficacy and safety.
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Bebidas , Citrus paradisi/química , Dieta , Interações Alimento-Droga , Alimentos , Voluntários Saudáveis , Piridonas/farmacocinética , Demografia , Humanos , Masculino , Piridonas/efeitos adversos , Equivalência Terapêutica , Adulto JovemRESUMO
1. Pitavastatin is an effective treatment for primary hyperlipidemia and mixed dyslipidemia. The aim of the present study was to investigate the effect of food on the pharmacokinetic properties and bioequivalence of the original, branded, formulation of pitavastatin calcium and a new generic formulation in healthy Chinese male subjects under fasting and fed conditions. 2. Under fasting and fed conditions, 90% CIs of the geometric mean of generic/branded AUC0-48 h ratios were 92.2-102.4%, 93.1-104.5%, the ratios of ln(AUC0-∞) were 92.6-103.7%, 93.2-103.5%, and ln(Cmax) ratios were 90.7-110.3%, 84.7-100.8%, respectively. The generic and branded formulations were bioequivalent in terms of rate and extent of absorption under both the conditions. The average values of AUC0-48 h, AUC0-∞ and Cmax decreased noticeably following a high-fat breakfast. Values for AUC0-48 h were 87.69% and 83.7%, values for AUC0-∞ were 87.5% and 84.6%, and values for Cmax were 45.0% and 50.4% in subjects given the generic and branded preparations, respectively. The absorption of pitavastatin calcium tablets was delayed following a high-fat meal, with Tmax increasing by up to 2.43-fold. 3. Both formulations were generally well tolerated, with no serious adverse reactions reported. The newly developed generic formulation may provide a reliable alternative to the branded tablets for patients with primary hyperlipidemia or mixed dyslipidemia.
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Povo Asiático , Alimentos , Saúde , Quinolinas/farmacocinética , Adulto , Química Farmacêutica , Humanos , Masculino , Quinolinas/efeitos adversos , Quinolinas/sangue , Reprodutibilidade dos Testes , Equivalência Terapêutica , Adulto JovemRESUMO
1. 1-Triacontanol (TA) recently shows promising anti-tumor activity. The present study was aimed to develop a sensitive gas chromatography-tandem mass spectrometry method to explore the pharmacokinetic profiles, distribution and excretion of TA in Sprague-Dawley rats after oral administration of TA. Chromatography separation was performed on a HP-5MS column. 1-Octacosanal was used as the internal standard (IS). Quantification of TA and IS was carried out at m/z 495.6 â 97.0 and m/z 467.5 â 97.0, respectively, in positive electron ionization and multiple reaction monitoring mode. The pharmacokinetic parameters were calculated by non-compartmental analysis. 2. The area under concentration-time curve AUC0-6 h and AUC0-∞ for TA at 60 mg/kg were 87.737 ± 13.574 and 93.617 ± 17.62, respectively. The mean residence time was 3.25 ± 0.17 h. In addition, the elimination half-lives (t1/2) were (2.37 ± 1.23, 1.27 ± 0.49, 2.07 ± 0.93) h after single oral administration of 30, 60 and 120 mg/kg of TA. After oral administration, TA was extensively distributed in stomach and intestine. The majority of TA excreted via feces, and its accumulative excretion ratio during the period of 72 h was 26.68 ± 7.14%, but only 0.0023 ± 0.0015% and 0.0027 ± 0.0006% for urines and bile, respectively. The absolute bioavailability (F, %) of TA was about 2.0%.
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Medicamentos de Ervas Chinesas/farmacocinética , Álcoois Graxos/farmacocinética , Animais , Medicamentos de Ervas Chinesas/análise , Álcoois Graxos/análise , Fezes/química , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Distribuição TecidualRESUMO
1-Triacontanol (TA), a member of long chain fatty alcohol, has recently been received great attention owing to its antitumor activity. In this study, an accurate, sensitive and selective gas chromatography-tandem mass spectrometry method was developed and validated for the quantification of TA in beagle plasma using 1-octacosanal as the internal standard (IS) for the first time. With temperature programming, chromatographic separation was carried out on an HP-5MS column, using helium as carrier gas and argon as collision gas, both at a flow rate of 1 mL/min. TA was analyzed using positive ion electrospray ionization in multiple-reaction monitoring mode, with the precursor to product ion transitions of m/z 495.6 â 97.0 and m/z 467.5 â 97.0 for TA and the IS, respectively. The lower limit of quantitation, linearity, intra- and interday precision, accuracy, stability, extraction recovery and matrix effect of TA were within the acceptable limits. The validated method was successfully applied to a pharmacokinetic study of TA in beagles.
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Álcoois Graxos/sangue , Cromatografia Gasosa-Espectrometria de Massas/métodos , Animais , Cães , Álcoois Graxos/farmacocinética , Feminino , Masculino , Espectrometria de Massas em Tandem/métodosRESUMO
1. DN604 is a new platinum agent with encouraging anticancer activity. The present study was to explore the pharmacokinetic profiles, distribution and excretion of platinum in Sprague-Dawley rats after intravenous administration of DN604. A sensitive and selective inductively coupled plasma mass spectrometry (ICP-MS) method was established for determination of platinum in biological specimens. The pharmacokinetic parameters were calculated by a non-compartmental method. 2. The area under concentration-time curve AUC0-t and AUC0-∞ for platinum originating from DN604 at 10 mg/kg were 25.15 ± 1.29 and 28.72 ± 1.04 µg/hml, respectively. The mean residence time MRT was 36.59 ± 6.65 h. The volume of distribution Vz was 11.42 ± 2.49 l/kg and clearance CL was 0.18 ± 0.01 l/h/kg. In addition, the elimination half-life T1/2z was 44.83 ± 9.75 h. After intravenous administration of DN604, platinum was extensively distributed in most of tested tissues except brain. The majority of platinum excreted via urine, and its accumulative excretion ratio during the period of 120 h was 63.5% ± 7.7% for urine, but only 6.94% ± 0.11% for feces. 3. The satisfactory half-life, wide distribution and high excretion made this novel platinum agent worthy of further research and development.
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Antineoplásicos/farmacocinética , Espectrometria de Massas/métodos , Platina/farmacocinética , Administração Intravenosa , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/urina , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Fezes/química , Platina/administração & dosagem , Platina/química , Platina/urina , Ratos Sprague-Dawley , Fatores de Tempo , Distribuição TecidualRESUMO
Triacontanol was confirmed to have a potential anti-cancer effect, the aim was to assess whether the co-administration of triacontanol alters the exposure of docetaxel via inducing hepatic CYP3A1/2 activity. The concentration of docetaxel in rats pretreated with triacontanol for seven successive days was determined, and the expression levels of CYP3A protein and mRNA were analyzed by the western blot and real time polymerase chain reaction (RT-PCR) technique, respectively. 2. The concentrations of docetaxel in rats pretreated with triacontanol were decreased, with 61.5%, 61.9% decrease in AUC0-24h and 65.7%, 54.9% reduction in Cmax (120 and 180 mg kg(-1), respectively) compared with the control. Hepatic clearance of docetaxel was enhanced in vitro and in vivo at dosage of 120 and 180 mg kg(-1), and CYP3A activity was up-regulated by measuring the formation rate of 1-hydroxymidazolam. Triacontanol preferentially induced protein expression level of CYP3A2 in a dose-dependent manner and of CYP 3A1 at dosage of 120 and 180 mg kg(-1). The mRNA expression of CYP3A1 was moderately different with the western blot results, but the trends appeared similar. CYP3A2 mRNA level was not markedly affected by triacontanol. 3. The significant triacontanol-docetaxel interaction was largely due to the induction of CYP3A1/2, which brought useful information in the clinical therapy when the combination is administered in human.
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Citocromo P-450 CYP3A/metabolismo , Álcoois Graxos/farmacologia , Taxoides/farmacocinética , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Área Sob a Curva , Citocromo P-450 CYP3A/genética , Docetaxel , Indução Enzimática/efeitos dos fármacos , Álcoois Graxos/administração & dosagem , Feminino , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Masculino , Microssomos Hepáticos/efeitos dos fármacos , Microssomos Hepáticos/metabolismo , Midazolam/análogos & derivados , Midazolam/metabolismo , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Taxoides/administração & dosagemRESUMO
Docetaxel (DTX) is a widely used anticancer drug for various solid tumors. However, its poor solubility in water and lack of specification are two limitations for clinical use. The aim of the study was to develop a thermosensitive chitosan/ß-glycerophosphate (C/GP) hydrogel loaded with DTX for intratumoral delivery. The in vitro release profiles, in vivo antitumor efficacy, pharmacokinetics, and biodistribution of DTX-loaded C/GP hydrogel (DTX-C/GP) were evaluated. The results of in vitro release study demonstrated that DTX-C/GP had the property of controlled delivery for a reasonable time span of 3 weeks and the release period was substantially affected by initial DTX strength. The antitumor efficacy of DTX-C/GP was observed at 20 mg/kg in H22 tumor-bearing mice. It was found that the tumor volume was definitely minimized by intratumoral injection of DTX-C/GP. Compared with saline group, the tumor inhibition rate of blank gel, intravenous DTX solution, intratumoral DTX solution, and DTX-C/GP was 2.3%, 29.8%, 41.9%, and 58.1%, respectively. Further, the in vivo pharmacokinetic characteristics of DTX-C/GP correlated well with the in vitro release. DTX-C/GP significantly prolonged the DTX retention and maintained a high DTX concentration in tumor. The amount of DTX distributed to the normal tissues was minimized so that the toxicity was effectively reduced. In conclusion, DTX-C/GP demonstrated controlled release and significant efficacy and exhibited potential for further clinical development.
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Antineoplásicos Fitogênicos/farmacocinética , Quitosana/farmacocinética , Glicerofosfatos/farmacocinética , Hidrogéis/farmacocinética , Taxoides/farmacocinética , Animais , Docetaxel , Masculino , Camundongos , Camundongos Endogâmicos ICR , Distribuição TecidualAssuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Acatisia Induzida por Medicamentos/tratamento farmacológico , Antipsicóticos/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Olanzapina/efeitos adversos , Propranolol/efeitos adversos , Esquizofrenia/tratamento farmacológico , Sonambulismo/induzido quimicamente , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Background: Front-line nurses have played a critical role during the coronavirus disease 2019 (COVID-19) pandemic. A number of qualitative studies reported front-line nurses' experiences and needs in caring for patients with COVID-19. However, the application of evidence from a single qualitative study to guide clinical practice has limitations. This study aimed to explore front-line nurses' experiences and needs during the COVID-19 pandemic through a qualitative meta-synthesis. Methods: Seven databases were searched from 1 December 2019 to 20 January 2022, including PubMed, Web of Science, Cochrane COVID-19 study register, CINAHL, PsycINFO, MedRxiv, and bioRxiv. The quality of included studies was appraised using the Critical Appraisal Skills Program (CASP) qualitative research appraisal tool. Meta-synthesis was used to synthesize the data from included studies. Results: A total of 70 studies were included, and five synthesized findings were developed: (1) Although nurses actively devoted themselves to fighting against COVID-19, considering their professional responsibility and historical previous experience with mankind, they were not invulnerable; (2) There were various difficulties and challenges in caring for patients with COVID-19, including fear related to providing patients with care, shortage of protective equipment and manpower, and negative attitude of family members; (3) Facing difficulties and challenges, nurses could only partly cope by using mixed means to overcome those, including media, learning, gaining skills, responding together, and organizational assistance; (4) To better respond to the COVID-19 pandemic, nurses' needs should be paid attention to. Counseling, training, information, resources, and investment are pivotal; (5) Despite the hardships, nurses became stronger and gained gratitude, positivity, mental peace, and confidence. Conclusions: This study reveals that the psychological experiences of front-line nurses varied, and they faced a variety of challenges. Although nurses had some coping strategies, they still needed multifaceted support to meet the challenges. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, PROSPERO: CRD42021255468.
Assuntos
COVID-19 , Pandemias , Aconselhamento , Humanos , Pesquisa QualitativaRESUMO
The problem of bacteria-induced infections threatens the lives of many patients. Meanwhile, the misuse of antibiotics has led to a significant increase in bacterial resistance. There are two main ways to alleviate the issue: one is to introduce antimicrobial agents to medical devices to get local drug releasing and alleviating systemic toxicity and resistance, and the other is to develop new antimicrobial methods to kill bacteria. New antimicrobial methods include cationic polymers, metal ions, hydrophobic structures to prevent bacterial adhesion, photothermal sterilization, new biocides, etc. Biodegradable biocompatible synthetic polymers have been widely used in the medical field. They are often used in tissue engineering scaffolds as well as wound dressings, where bacterial infections in these medical devices can be serious or even fatal. However, such materials usually do not have inherent antimicrobial properties. They can be used as carriers for drug delivery or compounded with other antimicrobial materials to achieve antimicrobial effects. This review focuses on the antimicrobial behavior, preparation methods, and biocompatibility testing of biodegradable biocompatible synthetic polymers. Degradable biocompatible natural polymers with antimicrobial properties are also briefly described. Finally, the medical applications of these polymeric materials are presented.