Population pharmacokinetics of diethylcarbamazine in patients with lymphatic filariasis and healthy individuals

The objective of this study was to develop a population pharmacokinetic model for DEC in subjects infected with lymphatic filariasis (LF) compared to healthy individuals, and to evaluate the effect of covariates on the volume of distribution (V/F) and oral clearance (CL/F) of DEC. This was an open-label cohort study of treatment naïve Wuchereria bancrofti-infected (n=32) and uninfected (n=24) adults residing in the Agboville district of Côte d'Ivoire. The population pharmacokinetic model for DEC was built using Phoenix NLME 8.0 software. The covariates included in the model building process were age, gender, bodyweight, infection status, creatinine clearance (CrCl), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. A total of 56 adults were enrolled in the study and a total of 728 samples were obtained over 168 hours. A one-compartment linear pharmacokinetic model with first-order absorption with an absorption lag-time (Tlag) best described the data. After determining the pharmacokinetics (PK) parameters of DEC, body weight and gender were found to be the significant covariates for DEC V/F. The final population pharmacokinetic model adequately described the pharmacokinetics of DEC in the studied population. Model-based simulation indicated that the body weight significantly impacted the exposure in both the male and female population. This analysis may further support the drug-drug interaction model development of DEC with different co-administered...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Source Type: research