Population Pharmacokinetics of the Antimalarial Amodiaquine: A Pooled Analysis to Optimize Dosing.

Population Pharmacokinetics of the Antimalarial Amodiaquine: A Pooled Analysis to Optimize Dosing. Antimicrob Agents Chemother. 2018 Jul 23;: Authors: Ali AM, Penny MA, Smith TA, Workman L, Sasi P, Adjei GO, Aweeka F, Kiechel JR, Jullien V, Rijken MJ, McGready R, Mwesigwa J, Kristensen K, Stepniewska K, Tarning J, Barnes KI, Denti P, WWARN amodiaquine PK study group Abstract Amodiaquine plus artesunate is the recommended antimalarial treatment in many malaria-endemic countries. However, pediatric doses are largely based on a linear extrapolation from adult doses. We pooled data from previously published studies on the pharmacokinetics of amodiaquine, to optimize the dose across all age groups. Adults and children with uncomplicated malaria received daily weight-based doses of amodiaquine or artesunate-amodiaquine over three days. Plasma concentration-time profiles for both parent drug and metabolite were characterized using nonlinear mixed-effects modelling. Amodiaquine pharmacokinetics was adequately described by a two-compartment disposition model, with first-order elimination leading to the formation of desethylamodiaquine, which was best described by a three-compartment disposition model. Body size and age were the main covariates affecting amodiaquine clearance. After adjusting for the effect of weight, clearance rates for amodiaquine and desethylamodiaquine reached 50% of adult maturation at 2.8 (95% CI: 1.5 - 3.7) and 3.9 (95%...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research