Population pharmacokinetics of cyclosporine in mexican pediatric patients with renal transplants

Abstract

Statement of Purpose, Innovation or Hypothesis: The purpose of the study was to determine the population pharmacokinetic (PPK) of cyclosporine (CsA) in children subjected to renal transplant. Description of Methods and Materials: The study was conducted from 1948 retrospective drug monitoring data points were collected from 54 renal pediatric patients receiving CsA. For the structural model (PPK) the MONOLIX 1 MLXTRANS program was used, the data were fitted using a two-compartment model with first order kinetics. The structural model was selected according to the best fit, according to criteria of-2Log likelihood, Akaike and Bayesian models. Data and Results: To assess the effect of covariates on the response we carried out PPK correlation between parameters: Ka, Vd, K12, K21 and Ke with the variables of interest: age (months), sex, body mass index (BMI, kg/m2), current weight (kg), comprising postoperative days (POD), creatinine clearance (CrCl, mL/min), transplant rejection, and nutritional status (NS). Population values obtained were Ka/F ¼ 0.157 0.049(h-1); Vd/F ¼ 0.323 0.064 (Vd/F/70Kg) (L); Ke/F ¼ 0.145 0.03 (h-1); K12 ¼ 7.58 23 (h-1) and K21 ¼ 26.3 79 (h-1). In assessing the influence of covariates of interest on the PPK of CsA, it was determined that the actual weight, the CrCl, the (RT) and (NS), showed significant correlation with Vd, and consequently with the CsACL, which determines interindividual variability. In order to correct for the influence of variables over response, we used the following equation: Vd/F/70 ¼ 0323-0508 (CrCl-74) -0539(WT-37.5)-0562 0566 POD-NS-0456 RT (L/70Kg). Interpretation, Conclusion or Significance: In summary, the population pharmacokinetics model developed for CsA after administration in pediatric renal transplant patients was validated. The model obtained for CsA PPK can be useful for dose adjustment in pediatric Mexican patients, aimed at achieving therapeutic optimization of CsA