Population pharmacokinetics of pyrimethamine and sulfadoxine in children with congenital toxoplasmosis

Publisher Website
Google Scholar
Abstract
Aims: To develop a population pharmacokinetic model for pyrimethamine (PYR) and sulfadoxine (SDX) in children with congenital toxoplasmosis.Methods: Children were treated with PYR (1.25 mg kg−1) and SDX (25 mg kg−1) (Fansidar®) plus folinic acid (Lederfoline® 5 mg). Plasma concentrations, available from a therapeutic drug monitoring database, were determined by high‐performance liquid chromatogrphy. Population pharmacokinetic analysis was performed using a nonlinear mixed effects model.Results: Eighty‐nine children, aged 1 week to 14 years and weighing 2.9–59 kg, were available for evaluation. Both PYR and SDX concentration‐time profiles were best described by a one‐compartment open model. Volume of plasma distribution (V) and clearance (CL) were significantly related to body weight (BW) using an allometric function. Typical CL and V estimates (95% confidence interval), for a child weighing 11 kg were 5.50 (5.28, 5.73) l day−1 and 36 (33, 39) l for PYR and 0.26 (0.25, 0.27) l day−1 and 2.1 (1.9, 2.3) l for SDX. For BW between 3.5 and 60 kg, plasma half‐lives were predicted to vary from 4.0 to 5.2 days for PYR, and from 5.0 to 7.5 days for SDX.Conclusion: This study indicated that body weight influences PYR and SDX pharmacokinetics in children. To optimize PYR/SDX combination treatment in congenital toxoplasmosis, short dosing intervals in very young low‐wight children are probably appropriate.