FARMACOCINÉTICA POBLACIONAL DE LOPINAVIR/RITONAVIR EN PACIENTES INFECTADOS CON VIH Y SU POSIBLE CORRELACIÓN CON LA EXCRECIÓN URINARIA DEL 6ßOHCORTISOL/CORTISOL

Abstract

The progressive development of resistance to the antiretroviral agents makes difficult to control the patologic infection and requires to increase the amount of optimization for its clinical practice. The right amount of dosage the main key to reach this goal. The separation of the therapy with the protease inhibitors seems to be necessary as shown in recently studies published where it shows the wide variability inter and intraindividual in the pharmacokinetics parameters of this group of drugs. The combination of lopinavir and ritonavir (LPV/RTV), are two protease inhibitors of HIV, used a lot with the antiretroviral treatment. In our investigation we developed two different population model in one hand our first Farmacocinética Poblacional de lopinavir/ritonavir en pacientes con VIH ESM-IPN 17 model (LPV) described the variability of pharmacokinetics of lopinavir in presence of ritonavir in mexican patients infected with HIV, in the other hand our second model described properly the variability of pharmacokinetics in ritonavir. The data was analyzed using a model "Nonlinear of mixed effects model” in the program NONMEM. The analysis included 50 patients HIV positive, in the treatment with LPV/RTV (400/100 mg). The data was described by one compartment model with absorption and elimination of first order for both models. The covariables tested in the model for lopinavir were age, weight, size, gender, concentration of ritonavir inhibitor, relation of 6BOHCortiol/cortisol. The population model developed of lopinavir the following parameters were: CL/FLPV 11.85 L/h, Vd/FLPV= 42.91 L y Ka LPV= 2.42 h-1, con una variabilidad interindividual de 146%, 36.19% y 36.87% respectivamente. In the other hand population model of ritonavir the following parameter were obtained: CL/FRTV 42.8 L/h, Vd/FRTV= 133 L y Ka RTV= 0. 18h-1 (Fix) with a interindividual variability of 44.83%, 81.24% and 0.45% respectively. The population pharmacokinetics models of lopinavir and ritonavir developed can help to predict the levels of concentration of LPV/RTV and individualize the regimes of dosage of LPV/RTV in any population of mexican patients infected with HIV, based on knowing the weight and gender, however, the clinical transcendency of our final model should be explore through a prospective study in which the model is used to adjust the dosage of lopinavir in presence of ritonavir.