RESUMEN
The aim of the present work was to evaluate the antidepressant like-effect and plasma concentration of Sertraline (SRT) using an inclusion complex (IC) with ß-cyclodextrin (ßCD) in mice. This supramolecular system was prepared using two different molar ratios at 1:1 and 1:2 SRT:ßCD and both were characterized to assess the drug inclusion into the host cavity. Based on the X-ray powder diffraction, Fourier transform infrared spectroscopy and thermal analysis the interaction between host and guest molecules could be suggested. This result indicates that the freeze drying process was efficient to prepare the ICs, when these are compared with the physical mixtures. By comparing the solid state results of 1:1 and 1:2 ICs no significant chemical or structural changes were identified between these systems. However, in vivo experiments indicated that the host-guest ratio was able to modify the SRT activity. Mice treated with both ICs (20 mg kg(-1), p.o.) have shown lower immobility time in the tail suspension test in comparison with mice treated with free SRT (20 mg kg(-1), p.o.). Mice spontaneous locomotor activity was not affected by any treatment. Higher SRT plasma concentration was determined after 30 min of treatment with 1:1 IC in comparison with free SRT, demonstrating the IC greater drug transport efficacy.
Asunto(s)
Antidepresivos/farmacología , Sertralina/farmacología , beta-Ciclodextrinas/farmacología , Animales , Antidepresivos/sangre , Antidepresivos/química , Suspensión Trasera , Masculino , Ratones , Actividad Motora/efectos de los fármacos , Difracción de Polvo , Sertralina/sangre , Sertralina/química , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X , beta-Ciclodextrinas/químicaRESUMEN
UNLABELLED: Enalapril maleate, available on the market in a variety of different pharmaceutical formulations, is commonly used for the control of systemic arterial hypertension. Many therapeutical failures have been reported thus far in clinical practice with respect to switching between different pharmaceutical formulations of the same product during pharmacological therapy. In the present study, plasma concentrations of enalapril and enalaprilate were measured in hypertensive patients undergoing treatment with different pharmaceutical formulations. MATERIALS AND METHODS: Pharmaceutical formulations studied included the reference brand product, a generic formulation, and a third drug product marketed as "similar"; plasma samples were obtained from 30 hypertensive volunteer patients. Drug was extracted from the plasma by solid phase extraction and determined by liquid chromatography-tandem mass spectrometry. The method was validated for the main analytical parameters. RESULTS: The analytical method developed in this study, using liquid chromatography-tandem mass spectrometry, was confirmed as suitable for application in the determination of plasma concentrations in patients and subsequently revealed statistically significant differences in plasma concentrations between the 3 treatment groups. CONCLUSIONS: Such differences reinforce the hypothesis that the bioequivalence tests currently proposed by the regulatory authorities to promote interchangeability between pharmaceutical formulations may not in fact represent a definitive parameter for guaranteeing similar plasma concentrations.
Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/sangre , Química Farmacéutica/estadística & datos numéricos , Cromatografía Líquida de Alta Presión/métodos , Enalapril/sangre , Enalaprilato/sangre , Hipertensión/sangre , Espectrometría de Masas en Tándem/métodos , Inhibidores de la Enzima Convertidora de Angiotensina/farmacocinética , Calibración , Enalapril/metabolismo , Enalapril/farmacocinética , Humanos , Hipertensión/tratamiento farmacológico , Límite de Detección , Reproducibilidad de los Resultados , Extracción en Fase Sólida , Espectrometría de Masa por Ionización de Electrospray , Equivalencia TerapéuticaRESUMEN
A specific high performance liquid chromatography-mass spectrometric (LC-MS/MS) assay was developed for the determination of captopryl in plasma. The retention time was 1.45 and 1.37 min for captopril and enalapril, respectively. The overall mean recovery, using SPE extraction with OASIS HLB cartridges, was found to be 107.2+/-9.5 and 100.04+/-2%, respectively. Calibration curves were linear in the concentration range of 10.00-2000.00 ng/ml, and the lower limit of quantification (LLOQ) was 10.00 ng/ml. The LLOQ was sensitive enough for detecting terminal phase concentrations of the drug. Inter-batch precision of the method ranged from 0.88 to 1.95%. Intra-batch accuracy ranged from 97.15 to 105.77%, while intra-batch precision ranged from 2.49 to 5.66% at concentrations of 30.00, 760.00 and 1500.00 ng/ml. The developed method was applied to study bioequivalence of captopril in a group of 25 human subjects at a single oral dose of a 50mg tablet.