Farmacocinética do efavirenz em coelhos: estudo comparativo do insumo farmacêutico ativo e dispersão sólida polimérica
Carregando...
Data
2018-02-08
Autores
Oliveira, Jonata Augusto
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
O efavirenz (EFZ), fármaco de primeira escolha utilizado no tratamento da imunodeficiência adquirida, é um fármaco de Classe II segundo o Sistema de Classificação Biofarmacêutica. A baixa solubilidade desta classe de fármacos tem significativo impacto na sua absorção enteral, resultando principalmente em biodisponibilidade errática, característica que pode contribuir para a variabilidade de resposta ao tratamento. Frente a esse problema, o Laboratório de Tecnologia de Medicamentos (LTM) da Universidade Federal de Pernambuco complexou o EFZ em dispersão sólida (DS) com o objetivo de aumentar sua solubilidade e melhorar suas características de absorção. Para avaliar os resultados dessa inovação, o estudo da disposição cinética na administração por diferentes vias e diferentes modelos animais é indicado. Neste sentido, o presente estudo teve como objetivo avaliar e comparar a farmacocinética pré-clínica do EFZ em coelhos albinos (machos; 2,8 kg; n=21) após administração intravenosa (2,7 mg/kg) e oral do insumo farmacêutico ativo (50 mg) e do EFZ carreado pela DS (50 mg – 10% EFZ). A quantificação de EFZ no plasma dos animais foi realizada através de método cromatográfico previamente validado e os parâmetros farmacocinéticos foram obtidos utilizando cálculos farmacocinéticos para modelo monocompartimental. O grupo EFZ-IV mostrou-se diferente estatisticamente em todos os parâmetros farmacocinéticos em relação às duas administrações orais; e esses resultados são esperados pois na administração intravenosa não há processo de absorção. Para os grupos ORAL-IFA e ORAL-DS não foram observadas diferenças estatísticas significativas entre os parâmetros farmacocinéticos, porém, foi observada menor variabilidade intra-grupo nesses parâmetros para o grupo que recebeu a dispersão sólida. Os resultados obtidos para ORAL-IFA e ORAL-DS de Cl 29,76 ± 73,33% e 21,75 ± 27,55% mL/min/kg; Vdárea 20,5 ± 83,93% e 11,6 ± 70,18% L/kg; t1/2 10 ± 94,85% e 6 ± 57,99 h; Cmax 1,46 ± 62,69% e 1,66 ± 48,20% µg/mL, respectivamente, mostram que o EFZ carreado pela DS contribui de forma positiva para diminuição da alta variabilidade das suas concentrações plasmáticas, fundamentando estudos futuros em outros modelos animais e posteriormente estudos clínicos, com o objetivo de implementa-lo na terapêutica.
Efavirenz (EFZ), the first-choice drug used to treat acquired immunodeficiency, is a Class II drug according to the Biopharmaceutical Classification System. The low solubility of this class of drugs has a significant impact on its enteral absorption, resulting mainly in erratic bioavailability, a characteristic that may contribute to the variability of response to treatment. Faced with this problem, the Laboratory of Medication Technology (LTM) of the Federal University of Pernambuco produced a new solid dispersion (DS) with the objective of increasing EFZ solubility and improving its absorption characteristics. To evaluate the results of this innovation, the kinetic arrangement in the administration by different routes and different animal models is indicated. The aim of the present study was to evaluate and compare the pre-clinical EFZ pharmacokinetics in albino rabbits (male, 2.8 kg, n = 21) after intravenous (2.7 mg/kg), oral active pharmaceutical ingredient (50 mg) and carried by DS (500 mg - 10% EFZ). EFZ quantification was performed using a previously validated chromatographic method and the pharmacokinetic parameters were obtained and compared to each other using pharmacokinetic calculations for one-compartmental models. The EFZ-IV group was statistically different in all pharmacokinetic parameters relative to the two oral administrations, these results are expected since intravenous administration does not undergo the absorption process, leading to the immediate occurrence of the distribution and elimination processes. For the ORAL-IFA and ORAL-DS groups, no statistically significant difference was observed either, but less intra-animal variability was observed in the pharmacokinetic parameters from administration carried out by solid dispersion. The results obtained for ORAL-IFA and ORAL-DS of Cl 29.76 ± 73.33% and 21.75 ± 27.55% mL/min/kg; Vdarea 20.5 ± 83.93% and 11.6 ± 70.18% L/kg; t1/2 10 ± 94.85% and 6 ± 57.99 h; Cmax 1.46 ± 62.69% and 1.66 ± 48.20% μg/mL, respectively, show that EFZ carried with DS contributes positively to decrease the high variability of its plasma concentrations, grounding future studies in other animal models and later clinical studies, with a view to its implementation in therapeutics.
Efavirenz (EFZ), the first-choice drug used to treat acquired immunodeficiency, is a Class II drug according to the Biopharmaceutical Classification System. The low solubility of this class of drugs has a significant impact on its enteral absorption, resulting mainly in erratic bioavailability, a characteristic that may contribute to the variability of response to treatment. Faced with this problem, the Laboratory of Medication Technology (LTM) of the Federal University of Pernambuco produced a new solid dispersion (DS) with the objective of increasing EFZ solubility and improving its absorption characteristics. To evaluate the results of this innovation, the kinetic arrangement in the administration by different routes and different animal models is indicated. The aim of the present study was to evaluate and compare the pre-clinical EFZ pharmacokinetics in albino rabbits (male, 2.8 kg, n = 21) after intravenous (2.7 mg/kg), oral active pharmaceutical ingredient (50 mg) and carried by DS (500 mg - 10% EFZ). EFZ quantification was performed using a previously validated chromatographic method and the pharmacokinetic parameters were obtained and compared to each other using pharmacokinetic calculations for one-compartmental models. The EFZ-IV group was statistically different in all pharmacokinetic parameters relative to the two oral administrations, these results are expected since intravenous administration does not undergo the absorption process, leading to the immediate occurrence of the distribution and elimination processes. For the ORAL-IFA and ORAL-DS groups, no statistically significant difference was observed either, but less intra-animal variability was observed in the pharmacokinetic parameters from administration carried out by solid dispersion. The results obtained for ORAL-IFA and ORAL-DS of Cl 29.76 ± 73.33% and 21.75 ± 27.55% mL/min/kg; Vdarea 20.5 ± 83.93% and 11.6 ± 70.18% L/kg; t1/2 10 ± 94.85% and 6 ± 57.99 h; Cmax 1.46 ± 62.69% and 1.66 ± 48.20% μg/mL, respectively, show that EFZ carried with DS contributes positively to decrease the high variability of its plasma concentrations, grounding future studies in other animal models and later clinical studies, with a view to its implementation in therapeutics.
Descrição
Palavras-chave
Efavirenz, Dispersão sólida, Farmacocinética, SIDA, Solid dispersion, Pharmacokinetics, AIDS