RESUMO
Se desarrolló un estudio de biodisponibilidad de metformina 850 mg tabletas recubiertas de liberación inmediata elaboradas por Laboratorios Coaspharma S.A., en 12 voluntarios sanos de ambos sexos, con edades entre 18 y 26 años. Para llevarlo a cabo se validó previamente un método bioanalítico para la determinación de metformina en plasma humano por cromatografía líquida de alta resolución con detector ultravioleta (HPLC-UV), el cual resultó ser selectivo, específico, lineal, exacto y preciso, por lo tanto adecuado para el análisis de las muestras. Estas fueron recolectadas periódicamente en un lapso desde 0 a 24 horas, luego de la administración por vía oral de una única dosis de metformina 850 mg. Posteriormente se determinaron los parámetros farmacocinéticos promedio de los 12 participantes, obteniendo: área bajo la curva, desde tiempo cero hasta el último tiempo de muestreo t (AUC0--->t) 6856,89 ± 2073,8 ng.h/ml, área bajo la curva desde tiempo cero hasta tiempo infinito (AUC0--->∞) 7083,74 ± 2131,52 ng.h/ml, concentración máxima (Cmaxmax) 1299,02 ± 291,90 ng/ml, tiempo máximo (t) 2,33 ± 0,47 h, tiempo de vida media (t1/2) 2,50 ± 0,84 h y constante aparente de eliminación (Ke) de 0,31 ± 0,12 h-1. Los resultados fueron similares en todos los participantes y no se produjeron reacciones adversas.
A bioavailability study was conducted in 12 healthy volunteers of both genders, aged between 18 and 26. Previous to the study, a bioanalytical method for determination of metformin in human plasma by high performance liquid chromatography with ultraviolet detector (HPLCUV) was validated, and proved to be selective, specific, linear, accurate precise, and therefore, suitable for analysis in plasma. Samples were collected from 0 to 24 hours after the oral administration of a single dose of metformin 850 mg immediate-release coated tablets, produced by Coaspharma S.A. Laboratories. Then, average pharmacokinetic parameters of the twelve volunteers were determined: area under the curve from time zero to last sampling time t (AUC0--->t) 6856.89 ± 2073.8 ng.h/mL, area under the curve from time zero to infinite time (AUC0--->∞) 7083.74 ± 2131.52 ng.h/ml, maximum concentration (Cmax) 1299.02 ± 291.90 ng/mL, maximum time (t max) 2.33 ± 0.47 h, half-life (t1/2) 2.50 ± 0.84 h and apparent elimination constant (Ke) of 0.31 ± 0.12 h-1. These results are similar between the volunteers and no adverse effect was observed. Also, the results are in agree with those reported in literature.
RESUMO
One of the most important aspects regarding the therapeutic efficacy of antimalarials is its quantification in biologic fluids. The detection and measurement of antimalarial drug levels is important for demonstrating (1) adequate absorption of the drug being given, (2) compliance in taking the full regimen required for treatment and (3) the level of drug in the blood at any time during the test period that parasites reappear. There is a lack of validated methods that simultaneously quantify different antimalarials administered at the same time, such as the use of chloroquine (CQ) and primaquine (PQ) in infections caused by Plasmodium vivax. In this study, a bioanalytical method was validated for the simultaneous quantification of primaquine (PQ), chloroquine (CQ) and desethylchloroquine (DSCQ) in human plasma using liquid-liquid extraction and high performance liquid chromatography with a diode array detector (HPLC-DAD). The PQ was evaluated over a concentration range of 100-3000 nM and the CQ and DSCQ was evaluated over a concentration range of 20-2000 nM. The selectivity of the method was verified by checking for interference by commonly used antimalarials and plasma samples. The accuracy and precision of the method was assessed for drugs spiked into human plasma and recoveries of 83.7%, 92.3%, and 76.5% were obtained for CQ, DSCQ, and PQ, respectively. The applicability of this method was also demonstrated with blood samples from patients with vivax malaria that received combination CQ plus PQ treatment. The simultaneous detection and accurate measurement of CQ, DSCQ, and PQ levels in human plasma provides an important and economical method for validating and monitoring sensitivity/resistance of P. vivax to more common treatment regimen.
