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1.
J Environ Sci Health B ; 55(11): 990-1001, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32877275

RESUMO

Application of municipal biosolids in agriculture present a concern with potential uptake and bioaccumulation of pharmaceutical compounds from biosolids into agronomic plants. We evaluated the efficacy of biochar as a soil amendment to minimize uptake of antimicrobial agents (ciprofloxacin, triclocarban, and triclosan) in lettuce (Lactuca sativa) and carrot (Daucus carota) plants. Biochar reduced the concentration of ciprofloxacin and triclocarban in lettuce leaves and resulted in a 67% reduction of triclosan in carrot roots. There was no substantial difference in pharmaceutical concentrations in carrot and lettuce plant matter at low (2.0 g kg-1 soil) and high (20.4 g kg-1 soil) rates of applied biochar. The co-amendment of biochar and biosolids increased soil pH and nutrient content which were positively correlated with an increase in lettuce shoot biomass. Our results demonstrate the potential efficacy of using walnut shell biochar as a sorbent for pharmaceutical contaminants in soil without negatively affecting plant growth.


Assuntos
Carbanilidas/farmacologia , Carvão Vegetal , Ciprofloxacino/farmacologia , Daucus carota/efeitos dos fármacos , Alface/efeitos dos fármacos , Triclosan/farmacocinética , Agricultura/métodos , Anti-Infecciosos/farmacocinética , Biomassa , Biossólidos , Daucus carota/crescimento & desenvolvimento , Daucus carota/metabolismo , Alface/crescimento & desenvolvimento , Alface/metabolismo , Folhas de Planta/química , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/metabolismo , Raízes de Plantas/química , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Brotos de Planta/efeitos dos fármacos , Solo/química , Poluentes do Solo/análise , Poluentes do Solo/farmacocinética
2.
Int J Nanomedicine ; 15: 6225-6237, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32884271

RESUMO

Background: The realization of multifunction in one bulk material is fascinating for developing a new generation of devices. Quaternary phosphorus salts were seldom utilized as templates in haloargentate systems, and the hybridization of alkyl(triphenyl)phosphonium with halometallate will be a good strategy for the development of multifunctional material, especially for biological material. Methods: Under the template of (triphenyl)phosphonium-based quaternary phosphorus salts with different spacer lengths (n=2, 3, 4), three bromoargentate hybrids were constructed via the solution method, ie, (1,2-DBTPP)(Ag2Br4) (1), {(1,3-DBTPP)2(Ag7Br11)]∙CH3CN∙H2O} n (2), and {[(1,4-DBTPP)(Ag5Br7)](CH3CN)2∙H2O} n (3) (1,2-DBTPP2+=ethane-1,2-diylbis (triphenyl)phosphonium, 1,3-DBTPP2+=propane-1,3-diylbis (triphenyl)phosphonium, 1,4-DBTPP2+=butane-1,4-diylbis (triphenyl)phosphonium)). Results: The (Ag7Br11) n 4n- chain in 2 is a new type of 1-D bromoargentate chain constructed from cubane-like Ag4Br4 nodes, AgBr4 tetrahedrons and AgBr3 triangles. Interestingly, by elongating spacer n from 2 to 4, argentophilicity interactions are weakened, and the hydrogen bonds are strengthened. Consequently, their water stabilities and photocurrents are improved, in which the Ag-4d/Br-4p to π* anti-bonding orbital of the quaternary phosphorus transfer is facilitated. Furthermore, the greenish blue emissions can be detected. Finally, high inhabitation rates against Streptococcus mutans and Candida albicans can be observed in 2 and 3. Conclusion: In all experiments, by elongating the spacer lengths of quaternary phosphorus salts, multifunctions were integrated in the quaternary phosphorus/bromoargentate hybrids, including greenish blue luminescence, repeatable photocurrent responses and durable antimicrobial activities with enhanced water stability. This work could provide a theoretical guide for the design of new biologically multifunctional materials.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Compostos de Bromo/química , Ácidos Graxos/química , Fósforo/química , Anti-Infecciosos/farmacocinética , Compostos de Bromo/farmacologia , Candida albicans/efeitos dos fármacos , Cristalografia por Raios X , Estabilidade de Medicamentos , Ácidos Graxos/farmacologia , Luminescência , Testes de Sensibilidade Microbiana , Estrutura Molecular , Processos Fotoquímicos , Streptococcus mutans/efeitos dos fármacos , Água/química
3.
Biochim Biophys Acta Biomembr ; 1862(11): 183443, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32810490

RESUMO

Antimicrobial peptides are small molecules that display antimicrobial activity against a wide range of pathogens. In a previous work, by using model membranes we studied P6, a peptide that shows no antimicrobial activity, and P6.2, which exhibits antibacterial activity. In the present work we aimed to unravel the mode of action of these peptides by studying their interaction in vivo with Escherichia coli and Staphylococcus aureus. In this sense, to study the interactions with bacterial cells and their effect on the bacterial surface, zeta potential, spectroscopic, and microscopic methodologies were applied. P6.2 exhibits a higher affinity toward both bacterial envelopes. The ability of both peptides to disrupt afterwards the bacterial membrane was also studied. Both peptides were able to induce bacterial membrane damage, but higher concentrations of P6 were needed to obtain results comparable to those obtained for P6.2. Additionally, P6.2 exhibited faster damage kinetics. Altogether, these data allow postulating, in a physiologic model, that the lower affinity of P6 for bacterial envelope results in a minor final concentration of the peptide in the bacterial membrane unable to trigger the antimicrobial activity. Finally, the fact that the active P6.2 has the same MIC value for the Gram-positive and Gram-negative bacteria tested, but not the same profile in the permeabilization assays, reinforces the question of whether cell wall components act as electrostatic barriers preventing or minimizing membrane-active AMPs lethal action at the membrane level.


Assuntos
Anti-Infecciosos , Peptídeos Catiônicos Antimicrobianos , Membrana Celular , Escherichia coli/metabolismo , Modelos Químicos , Staphylococcus aureus/metabolismo , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacocinética , Peptídeos Catiônicos Antimicrobianos/farmacologia , Membrana Celular/química , Membrana Celular/metabolismo
4.
Clin Pharmacol Ther ; 108(5): 976-984, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32531808

RESUMO

We use a mechanistic lung model to demonstrate that accumulation of chloroquine (CQ), hydroxychloroquine (HCQ), and azithromycin (AZ) in the lungs is sensitive to changes in lung pH, a parameter that can be affected in patients with coronavirus disease 2019 (COVID-19). A reduction in pH from 6.7 to 6 in the lungs, as observed in respiratory disease, led to 20-fold, 4.0-fold, and 2.7-fold increases in lung exposure of CQ, HCQ, and AZ, respectively. Simulations indicated that the relatively high concentrations of CQ and HCQ in lung tissue were sustained long after administration of the drugs had stopped. Patients with COVID-19 often present with kidney failure. Our simulations indicate that renal impairment (plus lung pH reduction) caused 30-fold, 8.0-fold, and 3.4-fold increases in lung exposures for CQ, HCQ, and AZ, respectively, with relatively small accompanying increases (20 to 30%) in systemic exposure. Although a number of different dosage regimens were assessed, the purpose of our study was not to provide recommendations for a dosing strategy, but to demonstrate the utility of a physiologically-based pharmacokinetic modeling approach to estimate lung concentrations. This, used in conjunction with robust in vitro and clinical data, can help in the assessment of COVID-19 therapeutics going forward.


Assuntos
Azitromicina/farmacocinética , Infecções por Coronavirus , Hidroxicloroquina/farmacocinética , Pulmão , Pandemias , Pneumonia Viral , Anti-Infecciosos/farmacocinética , Antivirais/farmacocinética , Betacoronavirus/fisiologia , Disponibilidade Biológica , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/fisiopatologia , Relação Dose-Resposta a Droga , Desenho de Fármacos , Humanos , Concentração de Íons de Hidrogênio , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Taxa de Depuração Metabólica , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/metabolismo , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia
5.
Lancet Infect Dis ; 20(8): e181-e191, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32569625

RESUMO

Progressive antimicrobial resistance in Neisseria gonorrhoeae, Mycoplasma genitalium, and Trichomonas vaginalis has created a pressing need for treatment optimisations for sexually transmitted infections (STIs). In this Review, we aim to highlight urgent needs in global STI management, including: (1) improved surveillance to monitor antimicrobial resistance and clinical outcomes; (2) systematic pharmacokinetic and pharmacodynamic evaluations to ensure resistance suppression and bacterial eradication at all sites of infection; (3) development of novel, affordable antimicrobials; and (4) advancements in new molecular and point-of-care tests to detect antimicrobial resistance determinants. Antimicrobial resistance among STIs is a global public health crisis. Continuous efforts to develop novel antimicrobials will be essential, in addition to other public health interventions to reduce the global STI burden. Apart from prevention through safer sexual practices, the development of STI vaccines to prevent transmission is a crucial research priority.


Assuntos
Anti-Infecciosos/farmacocinética , Anti-Infecciosos/uso terapêutico , Resistência a Medicamentos , Doenças Sexualmente Transmissíveis/tratamento farmacológico , Humanos , Vigilância da População , Doenças Sexualmente Transmissíveis/microbiologia , Doenças Sexualmente Transmissíveis/parasitologia
6.
Clin Pharmacol Ther ; 108(5): 1090-1097, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32588427

RESUMO

Association between Hydroxychloroquine (HCQ) and Azithromycin (AZT) is under evaluation for patients with lower respiratory tract infection (LRTI) caused by the Severe Acute Respiratory Syndrome (SARS-CoV-2). Both drugs have a known torsadogenic potential, but sparse data are available concerning QT prolongation induced by this association. Our objective was to assess for COVID-19 LRTI variations of QT interval under HCQ/AZT in patients hospitalized, and to compare manual versus automated QT measurements. Before therapy initiation, a baseline 12 lead-ECG was electronically sent to our cardiology department for automated and manual QT analysis (Bazett and Fridericia's correction), repeated 2 days after initiation. According to our institutional protocol (Pasteur University Hospital), HCQ/AZT was initiated only if baseline QTc ≤ 480ms and potassium level> 4.0 mmol/L. From March 24th to April 20th 2020, 73 patients were included (mean age 62 ± 14 years, male 67%). Two patients out of 73 (2.7%) were not eligible for drug initiation (QTc ≥ 500 ms). Baseline average automated QTc was 415 ± 29 ms and lengthened to 438 ± 40 ms after 48 hours of combined therapy. The treatment had to be stopped because of significant QTc prolongation in two out of 71 patients (2.8%). No drug-induced life-threatening arrhythmia, nor death was observed. Automated QTc measurements revealed accurate in comparison with manual QTc measurements. In this specific population of inpatients with COVID-19 LRTI, HCQ/AZT could not be initiated or had to be interrupted in less than 6% of the cases.


Assuntos
Azitromicina , Infecções por Coronavirus , Monitoramento de Medicamentos , Eletrocardiografia/métodos , Hidroxicloroquina , Síndrome do QT Longo , Pandemias , Pneumonia Viral/tratamento farmacológico , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/farmacocinética , Azitromicina/administração & dosagem , Azitromicina/efeitos adversos , Azitromicina/farmacocinética , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Precisão da Medição Dimensional , Monitoramento de Medicamentos/instrumentação , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/normas , Feminino , Humanos , Hidroxicloroquina/administração & dosagem , Hidroxicloroquina/efeitos adversos , Hidroxicloroquina/farmacocinética , Síndrome do QT Longo/induzido quimicamente , Síndrome do QT Longo/diagnóstico , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , Torsades de Pointes/induzido quimicamente , Torsades de Pointes/prevenção & controle
7.
Mater Sci Eng C Mater Biol Appl ; 109: 110598, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32229004

RESUMO

This study highlights the incorporation of copper in the bioactive glasses (BAG) network that greatly influences the morphological, structural and biological properties. By increasing the copper incorporation in BAG, increment in cell volume was obtained from XRD patterns, and concomitantly, dominant phosphate bands and latent silica bands were observed by FT-IR and Raman spectroscopic results. The Cu addition also affected particle appearance to vary from spherical to cluster-like cubes in 1.5% and 2.5% copper-doped BAG. Due to the mesoporous network 1.5% and 2.5% copper-doped BAG showed enhanced release of anti-inflammatory drugs such as Acetaminophen (ACE) and Ibuprofen (IBU) in which, the drug release profiles showed best fit with kinetic models of First order, Korsmeyar-Peppas and Higuchi. Copper doping influences the lattice of BAG, as a result morphology and porosity varied, which regulates the ionic dissolution, hence, prompting bioactivity was perceived from 1.5% and 2.5% copper-doped bioactive glasses (Cu-BGs). Moreover, 2.5% Cu-BG and 1.5% Cu-BG showed highest rate of ROS detection, as well as improved antimicrobial activity. This study established that up to certain proportion of copper incorporation in BAG network, potentially enhances the biomineralization and turns the morphology towards minimal size with mesoporous nature. Due to the abundance in oral microbial exposure, copper amplifies the superior antimicrobial properties, and Cu-BGs act as a drug carrier to load ACE and IBU, which potentially up-regulate the healing properties in dental application.


Assuntos
Acetaminofen , Anti-Infecciosos , Bactérias/crescimento & desenvolvimento , Biomineralização/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Cobre , Portadores de Fármacos , Vidro/química , Ibuprofeno , Acetaminofen/química , Acetaminofen/farmacocinética , Acetaminofen/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/farmacologia , Cobre/química , Cobre/farmacocinética , Cobre/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Humanos , Ibuprofeno/química , Ibuprofeno/farmacocinética , Ibuprofeno/farmacologia
8.
J Vet Sci ; 21(2): e32, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32233138

RESUMO

Levofloxacin pharmacokinetic profiles were evaluated in 6 healthy female rabbits after intravenous (I/V), intramuscular (I/M), or subcutaneous (S/C) administration routes at a single dose of 5 mg/kg in a 3 × 3 cross-over study. Plasma levofloxacin concentrations were detected using a validated Ultra Performance Liquid Chromatography method with a fluorescence detector. Levofloxacin was quantifiable up to 10 h post-drug administration. Mean AUC0-last values of 9.03 ± 2.66, 9.07 ± 1.80, and 9.28 ± 1.56 mg/h*L were obtained via I/V, I/M, and S/C, respectively. Plasma clearance was 0.6 mL/g*h after I/V administration. Peak plasma concentrations using the I/M and S/C routes were 3.33 ± 0.39 and 2.91 ± 0.56 µg/mL. Bioavailability values, after extravascular administration were complete, - 105% ± 27% (I/M) and 118% ± 40% (S/C). Average extraction ratio of levofloxacin after I/V administration was 7%. Additionally, levofloxacin administration effects on tear production and osmolarity were evaluated. Tear osmolarity decreased within 48 h post-drug administration. All 3 levofloxacin administration routes produced similar pharmacokinetic profiles. The studied dose is unlikely to be effective in rabbits; however, it was calculated that a daily dose of 29 mg/kg appears effective for I/V administration for pathogens with MIC < 0.5 µg/mL.


Assuntos
Anti-Infecciosos/farmacocinética , Levofloxacino/farmacocinética , Testes de Sensibilidade Microbiana/veterinária , Coelhos/metabolismo , Animais , Estudos Cross-Over , Injeções Intramusculares/veterinária , Injeções Intravenosas/veterinária , Injeções Subcutâneas/veterinária
9.
Int J Mol Sci ; 21(4)2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32079131

RESUMO

The review collects together some recent information on the identity and pharmacological properties of magnoflorine, a quaternary aporphine alkaloid, that is widely distributed within the representatives of several botanical families like Berberidaceae, Magnoliaceae, Papaveraceae, or Menispermaceae. Several findings published in the scientific publications mention its application in the treatment of a wide spectrum of diseases including inflammatory ones, allergies, hypertension, osteoporosis, bacterial, viral and fungal infections, and some civilization diseases like cancer, obesity, diabetes, dementia, or depression. The pharmacokinetics and perspectives on its introduction to therapeutic strategies will also be discussed.


Assuntos
Aporfinas/química , Aporfinas/farmacologia , Descoberta de Drogas , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Antialérgicos/química , Antialérgicos/farmacocinética , Antialérgicos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/farmacologia , Antidepressivos/química , Antidepressivos/farmacocinética , Antidepressivos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacocinética , Antioxidantes/farmacologia , Aporfinas/farmacocinética , Metabolismo dos Carboidratos/efeitos dos fármacos , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Extratos Vegetais/farmacocinética , Plantas/química
10.
J Vet Pharmacol Ther ; 43(2): 179-188, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32039497

RESUMO

Biopharmaceutics Classification System (BCS) has gained broad acceptance in promoting the development of human drugs. To date, the applicability of existing human BCS criteria has not been evaluated in chickens. The objective of this study was to discuss the feasibility of BCS extrapolation between species and establish a preliminary chicken BCS by classifying seven veterinary commonly used drugs including metronidazole, amoxicillin, sulfamethoxazole, sulfadiazine, ciprofloxacin hydrochloride, doxycycline hydrochloride, and trimethoprim. Firstly, we finished the determination of physiological parameters affecting solubility in chickens, including body temperature, gastrointestinal pH, and the fluid volume in the gastrointestinal tract (GI), and the drug is considered highly soluble in chicken BCS when the highest dose strength is soluble in 20.40 ml (fed) or 6.73 ml (fasted) over the pH range of 1-8 at 41°C. Drug solubility classification was based on dose number calculation. Metronidazol and amoxicillin were classed differently under fed and fasted conditions. Secondly, we discussed the effect of ABC transporters (MDCK vs. MDCK-chAbcb1/Abcg2) and pH (5.5 vs. 7.4) on drug permeability and classification. The drug is classified as highly permeable when its permeability is equal to or greater than metoprolol tartrate. Though ABC transporters and pH significantly affected the permeability values of drugs (p < .05), the permeability classification of the drugs has not been changed except for sulfamethoxazole. This work highlights some of the significant challenges that would be encountered in order to develop a chicken BCS, this valuable information could serve as a helpful tool during chicken drugs development and to minimize the potential risks when developing formulations.


Assuntos
Anti-Infecciosos/classificação , Anti-Infecciosos/farmacocinética , Galinhas/metabolismo , Animais , Anti-Infecciosos/química , Transporte Biológico , Células CACO-2 , Cães , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Células Madin Darby de Rim Canino , Permeabilidade , Solubilidade
11.
Artigo em Inglês | MEDLINE | ID: mdl-31911204

RESUMO

This study was conducted to develop a highly selective, sensitive, and validated method for quantifying metronidazole in human plasma and bile fluid. Metronidazole and metronidazole-d4 (internal standard) were extracted from 100 µL of plasma and bile fluid by liquid-liquid extraction. Liquid chromatography with a Hydrosphere C18 column (50 × 2.0 mm) was performed using 10 mM ammonium formate (pH 4.0) and acetonitrile (20:80, v/v) as the mobile phase. Triple quadrupole mass spectrometry was operated with an electrospray ionization interface in multiple reaction monitoring and positive ion modes. The calibration curves were linear for bile and plasma samples over the range of 50-20,000 ng/mL (r2 > 0.999). The intra- and inter-day coefficients of variation (CVs) for plasma ranged from 2.50% to 7.85% and 3.11% to 16.9%, respectively; for bile, the intra-and inter-run precision (CVs) ranged from 2.76% to 13.2% and 3.16% to 11.5%, respectively. The mean extraction recovery for metronidazole ranged from 76.5% to 82.1% in plasma and from 78.8% to 87.8% in bile, respectively. Our proposed analytical method was successfully applied to determine metronidazole concentrations in bile as well as in plasma at multiple time points in a patient with acute cholangitis.


Assuntos
Bile/química , Cromatografia Líquida de Alta Pressão/métodos , Metronidazol/análise , Espectrometria de Massas em Tandem/métodos , Anti-Infecciosos/análise , Anti-Infecciosos/sangue , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Humanos , Limite de Detecção , Modelos Lineares , Extração Líquido-Líquido , Metronidazol/sangue , Metronidazol/química , Metronidazol/farmacocinética , Reprodutibilidade dos Testes
12.
Mater Sci Eng C Mater Biol Appl ; 108: 110337, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31923987

RESUMO

Biodegradable, biocompatible and non-toxic polymer-based nanoparticles are the novel nanotherapeutic tool which is used for adsorption and encapsulation drugs. Extended release formulation of Norfloxacin antibiotic, chemotherapeutic agent model, drug in the form of encapsulated and loaded poly (lactic acid) nanocomposites-based Titanium dioxide (PLA/TiO2) was developed. Nanocomposites were prepared using different contents (1, 3, 5 wt %) and morphologies of TiO2 (spheres (S), rods (R). The dispersion of TiO2 was aided by ultrasonic technique followed by solution casting method. The morphology, particle size, crystallite size and composition of the nanocomposites were examined by SEM, TEM, XRD and FTIR. The crystallinity and thermal behavior of the nanocomposites were characterized by DSC and TGA. NOR was loaded onto TiO2 nanospheres (NOR@TiO2 (S)) and the optimum conditions for loading was investigated. Pseudo-second order model was the more adequate to represent the kinetic data. The equilibrium data followed Freundlich adsorption isotherm and the adsorption process was exothermic. NOR@TiO2 (S) was encapsulated into PLA and in vitro release behavior of drug was compared with NOR adsorbed into PLA (NOR@PLA) and nanocomposites (NOR@PLA/TiO2) using different pH (6.7, 7.4) media. To study the mechanism of NOR release, first order, Higuchi, Hixon Crowell and Korsmeyer-Peppas models were applied on the experimental results. The cytotoxicity of the loaded nanocomposites using MTT assay was studied against HepG 2, MCF-7, HCT 116, PC-3, Hela, WI-38 and WISH cells. The encapsulated (NOR@ 5S/En PLA) showed the highest cytotoxic efficacy with moderate effect on normal cells. Moreover, the nanocomposites have great potential against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Salmonella and Klebsiella pneumonia. NOR@ PLA/TiO2 nanocomposites showed better antibacterial efficacy than NOR encapsulated nanocomposites. The nanocomposites could be effective vehicles for the sustained delivery of toxic anticancer drug.


Assuntos
Antineoplásicos , Nanocompostos , Neoplasias/tratamento farmacológico , Norfloxacino , Poliésteres , Titânio , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/farmacologia , Células HCT116 , Células HeLa , Células Hep G2 , Humanos , Células MCF-7 , Nanocompostos/química , Nanocompostos/uso terapêutico , Neoplasias/metabolismo , Neoplasias/patologia , Norfloxacino/química , Norfloxacino/farmacocinética , Norfloxacino/farmacologia , Células PC-3 , Poliésteres/química , Poliésteres/farmacocinética , Poliésteres/farmacologia , Titânio/química , Titânio/farmacocinética , Titânio/farmacologia
13.
Ophthalmic Res ; 63(1): 41-49, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31112980

RESUMO

PURPOSE: This study was aimed at determining the intraocular pharmacokinetics based on molecular physicochemical properties in a rabbit model. METHODS: The entire dataset was obtained from previous literature, and research articles regarding 70 molecular compounds were investigated. The intravitreal half-lives in rabbit eyeballs of 22 macromolecules and 48 micromolecules were analyzed. Multiple linear regression analysis was carried out with non-collinear independent variables (molecular weight [MW] and lipophilicity) influencing intravitreal half-lives. The best-fit equations were selected based on the correlation coefficients and goodness-of-fit statistics. RESULTS: The best-fit models obtained from the entire dataset, macromolecules, and micromolecules suggest the correlation between molecular physicochemical properties (MW and lipophilicity) and intravitreal half-life. Exclusion of outlier molecules (amphotericin B and foscarnet) leads to a better-fit correlation. MW is the definite single factor affecting intravitreal half-lives of macromolecules (Log t1/2 = 0.148 + 0.370 Log MW, R2 = 0.769), while both MW and lipophilicity influence the intraocular pharmacokinetics of micromolecules (Log t1/2 = -1.213 + 0.762 Log MW - 0.115 Log p, R2 = 0.554). CONCLUSION: The present study indicates that intravitreal half-life could be predicted based on molecular physicochemical properties (MW and lipophilicity). Also, increasing MW while reducing lipophilicity would be a reliable method for prolonging the intravitreal half-life of small chemical drugs, while MW is the single major determinant for large biologic drugs.


Assuntos
Inibidores da Angiogênese/farmacocinética , Anti-Infecciosos/farmacocinética , Anti-Inflamatórios/farmacocinética , Peso Molecular , Preparações Farmacêuticas/metabolismo , Corpo Vítreo/metabolismo , Animais , Injeções Intravítreas , Modelos Animais , Coelhos , Análise de Regressão
14.
Ann Pharmacother ; 54(5): 496-503, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31762287

RESUMO

Objective: To address the background and rationale for the recent introduction of the Modification of Diet in Renal Disease (MDRD) equation for renal dose adjustment of antimicrobials and to provide recommendations for pharmacists dosing new antimicrobial agents. Data Sources: Comprehensive MEDLINE and EMBASE literature searches (from August 2018 to October 2019) were performed. Search terms included creatinine clearance, Cockcroft-Gault, MDRD, and glomerular filtration rate and a subsequent search included the preceding terms AND antimicrobials OR antibiotics. Study Selection and Data Extraction: Available English-language studies on the derivation and/or use of the Cockcroft-Gault (CG) and MDRD study equation were evaluated as well as those that specifically discussed their use for dosing antimicrobial agents. Data Synthesis: The US Food and Drug Administration (FDA) approval of delafloxacin and meropenem-vaborbactam in 2017 ushered in a new era in renal dosing of antibiotics, in that both agents are recommended to be dosed by the MDRD equation. Studies demonstrate that the CG and MDRD equations can result in discrepant dosing recommendations. Relevance to Patient Care and Clinical Practice: The renal estimation equation recommended in a new antibiotic label should dictate the dosing of that medication. It is noteworthy that these equations are not interchangeable. Conclusion: Recently approved antimicrobials utilizing the MDRD equation for renal dose adjustment will be interspersed with old and new antimicrobials utilizing the CG equation because of lack of singular guidance by the FDA. This requires pharmacists to be vigilant in evaluating drug labels to determine which equation is recommended and to understand the differences, strengths, and limitations of each equation.


Assuntos
Anti-Infecciosos/administração & dosagem , Nefropatias/metabolismo , Nefropatias/fisiopatologia , Rim/efeitos dos fármacos , Adulto , Idoso , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/uso terapêutico , Creatinina/sangue , Desenvolvimento de Medicamentos , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Farmacêuticos , Estados Unidos , United States Food and Drug Administration
15.
Artigo em Inglês | MEDLINE | ID: mdl-31871085

RESUMO

Many antibiotics carry caution stickers that warn against alcohol consumption. Data regarding concurrent use are sparse. An awareness of data that address this common clinical scenario is important so health care professionals can make informed clinical decisions and address questions in an evidence-based manner. The purpose of this systematic review was to determine the evidence behind alcohol warnings issued for many common antimicrobials. The search was conducted from inception of each database to 2018 using PubMed, Medline via Ovid, and Embase. It included studies that involved interactions, effects on efficacy, and toxicity/adverse drug reactions (ADR) due to concomitant alcohol consumption and antimicrobials. All interactions were considered in terms of three components: (i) alteration in pharmacokinetics/pharmacodynamics (PK/PD) of antimicrobials and/or alcohol, (ii) change in antimicrobial efficacy, and (iii) development of toxicity/ADR. Available data support that oral penicillins, cefdinir, cefpodoxime, fluoroquinolones, azithromycin, tetracycline, nitrofurantoin, secnidazole, tinidazole, and fluconazole can be safely used with concomitant alcohol consumption. Data are equivocal for trimethoprim-sulfamethoxazole. Erythromycin may have reduced efficacy with alcohol consumption, and doxycycline may have reduced efficacy in chronic alcoholism. Alcohol low in tyramine may be consumed with oxazolidinones. The disulfiram-like reaction, though classically associated with metronidazole, occurs with uncertain frequency and with varied severity. Cephalosporins with a methylthiotetrazole (MTT) side chain or a methylthiodioxotriazine (MTDT) ring, ketoconazole, and griseofulvin have an increased risk of a disulfiram-like reaction. Alcohol and antimicrobial interactions are often lacking evidence. This review questions common beliefs due to poor, often conflicting data and identifies important knowledge gaps.


Assuntos
Álcoois/efeitos adversos , Álcoois/farmacocinética , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/farmacocinética , Azitromicina/efeitos adversos , Azitromicina/farmacocinética , Cefalosporinas/efeitos adversos , Cefalosporinas/farmacocinética , Doxiciclina/efeitos adversos , Doxiciclina/farmacocinética , Interações Medicamentosas , Eritromicina/efeitos adversos , Eritromicina/farmacocinética , Fluoroquinolonas/efeitos adversos , Fluoroquinolonas/farmacocinética , Metronidazol/efeitos adversos , Metronidazol/análogos & derivados , Metronidazol/farmacocinética , Penicilinas/efeitos adversos , Penicilinas/farmacocinética , Tetraciclina/efeitos adversos , Tetraciclina/farmacocinética
16.
Curr Drug Deliv ; 17(2): 112-125, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31880260

RESUMO

OBJECTIVE: The present study reports the use of MicrofluidizerTM technology to form a stable nanosuspension of atovaquone (ATQ) using quality by design (QbD) approach. METHODS: The patient-centric quality target product profile and critical quality attributes (CQAs) were identified. A Box-Behnken design was employed for the optimization of dependent variables, while CQAs like particle size and PDI were evaluated as response variables. Effective optimization of ATQ nanosuspension preparation using Microfluidizer processor as a novel green technology was achieved using QbD approach. RESULT: The prepared nanosuspension had a mean particle size of 865 nm ± 5%, PDI of 0.261 ± 3%, and zeta potential of -1.79 ± 5 mV. The characterization of the prepared nanosuspension by SEM, DSC, and XRD revealed its nano-crystalline nature whereas FTIR spectroscopic analysis confirmed the absence of any physicochemical interaction because of process parameters between the drug and excipients. CONCLUSION: In vitro dissolution studies of the nanosuspension using USP-IV exhibited a 100% cumulative drug release over 90 minutes, which is significantly better than that of ATQ pure API. In vivo pharmacokinetic studies revealed bioequivalence of ATQ nanosuspensions by Microfluidizer homogenization process to the marketed formulation1.


Assuntos
Anti-Infecciosos/química , Atovaquona/química , Animais , Anti-Infecciosos/farmacocinética , Atovaquona/farmacocinética , Disponibilidade Biológica , Desenho de Fármacos , Liberação Controlada de Fármacos , Masculino , Nanopartículas/química , Tamanho da Partícula , Ratos Sprague-Dawley , Solubilidade , Suspensões , Molhabilidade
17.
Int J Biol Macromol ; 144: 441-448, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31862374

RESUMO

The present study deals with novel synthesizing method of TEMPO oxidized cellulose (extracted from bagasse) (TOC) amino acids (l-phenyl alanine (Phe) and l-tryptophan (Trp)) nano-composites as potential antimicrobial biocompatible agents. The produced nanocomposites were characterized via Fourier transform Infrared (FT-IR) spectroscopy, thermal analysis (TGA and DTGA), scanning electron microscope(SEM), and transmission electron microscope (TEM) which approved that the synthesis of composites in nano-scale in spherical shape with average particle size 72 and 44.37 nm for l-phenylalanine composite (Phe-TOC) and l-tryptophan composite (Trp-TOC) respectively. The antimicrobial studies were carried out on (i) Gram-negative bacteria: Escherichia coli (NCTC-10416) and Pseudomonas aeruginosa (NCID-9016); (ii) Gram-positive bacteria: Streptococcus aurous (NCTC-7447) and Bacillus subtilis (NCID-3610); (iii) unicellular fungi: namely, Candida albicans (NCCLS 11). The results were cleared that the both composites have high effective, rapid and broad-spectrum antimicrobial activity. The Trp-TOC showed slightly higher antimicrobial activity than Phe-TOC especially in time required of killing performance. The Phe-TOC has required 20 h for killing all microbial population while Trp-TOC required only 12 h. The MIC values were close in both nanocomposites with high clear zone measurements in the same concentration in the case of Trp-TOC.


Assuntos
Anti-Infecciosos , Bactérias/crescimento & desenvolvimento , Candida albicans/crescimento & desenvolvimento , Celulose , Nanocompostos/química , Fenilalanina , Triptofano , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacocinética , Celulose/química , Celulose/farmacologia , Fenilalanina/química , Fenilalanina/farmacologia , Triptofano/química , Triptofano/farmacologia
18.
Ther Deliv ; 10(11): 697-717, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31789106

RESUMO

Nanogels have attracted considerable attention as nanoscopic drug carriers, particularly for site-specific or time-controlled delivery of bioactive mediators. A high diversity of polymer systems and the simple modification of their physicochemical features have provided multipurpose forms of nanogel preparations. Nanogels have outstandingly high stability, drug loading ability, biologic consistence, good permeation capability and can be responsive to environmental stimuli. Great potential has been shown by nanogels in many fields including delivery of genes, chemotherapy drugs, diagnosis, targeting of specific organs and several others. This review focuses mainly on different types of nanogels, methods of preparation including methods of drug loading, different modes of biodegradation mechanisms as well as main mechanisms of drug release from nanogels. Recent applications of nanogels are also briefly discussed and exemplified.


Assuntos
Materiais Biocompatíveis/química , Portadores de Fármacos/química , Composição de Medicamentos/métodos , Nanogéis/química , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/farmacocinética , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacocinética , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Química Farmacêutica , Reagentes para Ligações Cruzadas/química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Emulsões , Técnicas de Transferência de Genes , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Micelas , Modelos Animais , Tamanho da Partícula , Polimerização , Solubilidade , Vacinas/administração & dosagem , Vacinas/farmacocinética
19.
J Avian Med Surg ; 33(4): 361-368, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31833304

RESUMO

The pharmacokinetics of danofloxacin was investigated in rehabilitated California brown pelicans (Pelecanus occidentalis californicus) after a single intramuscular injection at a dose of 15 mg/kg body weight. The concentration of the drug in plasma was assayed by high-pressure liquid chromatography. A sparse-sampling design was used to reduce the number of samples (1-4 venipunctures) obtained from 24 brown pelicans. A population pharmacokinetic analysis with nonlinear mixed-effects modeling was used to accommodate the sparse-sampling strategy. The nonlinear mixed-effects modeling approach measured both fixed effects (typical values for the population) and random effects (between-subject variability) for this population. A 1-compartment model best represented the concentration-versus-time data after injection. After injection, the elimination half-life, peak concentration, area under the curve, and volume of distribution were 2.76 hours, 2.5 µg/mL, 13.75 µg/h/mL, and 4.35 L/kg, respectively. Rate of absorption was highly variable among the birds. The intramuscular injection of danofloxacin in pelicans at this dose produced plasma concentrations that meet therapeutic targets for bacteria with a minimum inhibitory concentration of ≤0.25 µg/mL. This dose can be used for future studies to evaluate the efficacy of danofloxacin for treating susceptible bacteria.


Assuntos
Anti-Infecciosos/farmacocinética , Aves/metabolismo , Fluoroquinolonas/farmacocinética , Animais , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/sangue , Área Sob a Curva , Cromatografia Líquida de Alta Pressão/veterinária , Fluoroquinolonas/administração & dosagem , Fluoroquinolonas/sangue , Meia-Vida , Injeções Intramusculares/veterinária , Absorção Intramuscular , Testes de Sensibilidade Microbiana/veterinária , Dinâmica não Linear , Músculos Peitorais/metabolismo
20.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 37(10): 626-633, dic. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-189588

RESUMO

INTRODUCTION: We analysed the changes in the susceptibility of Pseudomonas aeruginosa to antimicrobials over an 18-year period (2000-2017) in order to evaluate the adequacy of the antimicrobial therapy against this organism in patients admitted in a tertiary Spanish hospital (excluding the intensive care unit). In addition, the antimicrobial activity was evaluated using pharmacokinetic/pharmacodynamic (PK/PD) criteria as a microbiological surveillance tool. METHODS: Susceptibility was studied according to the Clinical and Laboratory Standards Institute breakpoints. Monte Carlo simulations were conducted to calculate the cumulative fraction of response (CFR). Linear regression analysis was applied to determine the trends in susceptibility and in the CFR. RESULTS: In 2017, susceptibility rates were: amikacin, penicillins and cephalosporins ≥ 85%, tobramycin 76%, meropenem 75% and gentamicin, imipenem and fluoroquinolones < 70%. PK/PD analyses was able to identify changes in antimicrobial activity not detected by only assessing MICs; meropenem administered in extended infusion attained a CFR > 90%, ceftazidime, piperacillin/tazobactam and imipenem provided CFRs between 80-90%, all of them administered at the highest doses. CONCLUSIONS: Analysis of susceptibility and PK/PD modelling, should be considered together to select the most appropriate antimicrobial drug and dosage regimen. Empirical antipseudomonal therapy would vary considerably if both microbiological surveillance tools were considered. In this study, the PK/PD analysis made it possible to preserve the therapeutic value of antimicrobials with low susceptibility rates, such as carbapenems, and the selection of the most effective antimicrobials among those with high rates of susceptibility


INTRODUCCIÓN: Para evaluar la terapia antimicrobiana frente a Pseudomonas aeruginosa (P. aeruginosa) en pacientes ingresados en un hospital terciario español (excluida Unidad de Cuidados Intensivos), se analizaron los cambios en la sensibilidad a los antimicrobianos durante 18 años (2000-2017). También se evaluó la actividad antimicrobiana utilizando criterios farmacocinéticos/farmacodinámicos (PK/PD) como herramienta de vigilancia microbiológica. MÉTODOS: La sensibilidad se estudió utilizando los puntos de corte del CLSI. Se realizaron simulaciones de Monte Carlo para calcular la fracción de respuesta acumulada (CFR). Se llevó a cabo un análisis de tendencia de sensibilidad y CFR mediante regresión lineal. RESULTADOS: En 2017, la sensibilidad a amikacina, penicilinas y cefalosporinas fue ≥ 85%; tobramicina 76%, meropenem 75% y para gentamicina, imipenem y fluoroquinolonas < 70%. El análisis PK/PD fue capaz de identificar cambios en la actividad antimicrobiana no detectados mediante la evaluación únicamente de las concentraciones mínimas inhibitorias; meropenem administrado en forma de infusión extendida alcanzó una CFR > 90%, ceftazidima, piperacilina/tazobactam e imipenem proporcionaron CFR entre 80 y 90%, todos ellos administrados a las dosis más altas. CONCLUSIÓN: La evaluación de la sensibilidad y el análisis PK/PD deben considerarse conjuntamente para seleccionar el tratamiento antimicrobiano más apropiado: fármaco y régimen de dosificación. La terapia empírica frente a P. aeruginosa variaría considerablemente si se consideraran ambas herramientas de vigilancia microbiológica. En este estudio, el análisis PK/PD ha permitido preservar el valor terapéutico de antimicrobianos con bajos valores de sensibilidad, como los carbapenems, y la selección de los antimicrobianos de mayor eficacia, entre aquellos que presentaban altos valores de sensibilidad


Assuntos
Humanos , Antibacterianos/farmacocinética , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Anti-Infecciosos/farmacocinética , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/isolamento & purificação , Modelos Lineares
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