Estudio de la interaccion entre ritonavir y saquinavir en su absorción intestinal / No disponible

El estudio se ha diseñado con objeto de determinarla interacción entre el ritonavir y el saquinavirdurante su absorción gastrointestinal.Para ello, se han realizado estudios de perfusiónen el intestino delgado completo de ratasWistar, con distintas proporciones de los dosfármacos. Los resultados obtenidos demuestranque la constante aparente de velocidad deabsorción (kap) del ritonavir disminuye, aunqueno significativamente, cuando la concentraciónde saquinavir es al menos un 40% superiora la de ritonavir. Asimismo, la kap saquinavirdisminuye cuando la concentración de ritonavires un 25% superior a la de saquinavir,si bien estas diferencias no son significativas.El mismo comportamiento se observa cuandola concentración de ritonavir es un 40% inferiora la de saquinavir, lo que indicaría que la incorporacióndel saquinavir se modifica por el ritonavir.Se requieren estudios adicionales paradilucidar el mecanismo concreto de interacciónentre los dos fármacos

The study has been designed in order to determinatethe interaction between the ritonavirand the saquinavir during its gastrointestinalabsorption. For it, perfusion studies have beencarried out in the whole intestine of the Wistarrats, with different proportions of the two drugs.The results obtained demonstrate that the apparentabsorption rate constant (kap) of the ritonavirit diminishes, although not significantly,when the saquinavir concentration is at least40% superior to that of ritonavir. Also, the kapsaquinavir diminishes when the ritonavir concentrationis 25% superior to that of saquinavir,although these differences are not significant.The same behavior is observed when the ritonavirconcentration is 40 % smaller to that ofsaquinavir, what would indicate that the incorporationof the saquinavir modifies for the ritonavir.Additional studies are required to elucidatethe concrete mechanism of interactionamong the two drugs

Use of nonlinear mixed effect modeling for the intestinal absorption data: application to ritonavir in the rat.

The aim of this study is to investigate in situ the mechanisms involved in the gastrointestinal absorption of ritonavir in the rat, as an animal model for preclinical studies of anti-HIV agents in vivo. Four ritonavir solutions (40, 27, 13 and 7 microM) in the presence of 1% dimethylsulfoxide (DMSO) were perfused in the small intestine of anaesthetised rats. Effects of DMSO on the intestinal permeability were investigated using solutions containing antipyrine 1.33 mM and ritonavir 7 microM with and without 1% of DMSO. Antipyrine and ritonavir transport was not modified in the presence of 1% of DMSO. The population pharmacokinetic parameters of the ritonavir intestinal transport were obtained by means of nonlinear mixed effect modelling approach according to a nonlinear absorption and nonlinear secretion. The absorption and secretion kinetic parameters for ritonavir were: Vm=47.6 microM/h; Km=8.77 microM; Vms=3.66 microM/h and Kms=0 microM. The interindividual variability found to ritonavir Vm 13.1%, and the residual variability was 8.98%. The Kms value support the saturation of the carrier at the range of concentrations of ritonavir assayed. The interindividual variability value of the Vm could explain, at least in part, the variability in absorption rate constants observed.