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. 2004 Jun;57(6):735-41.
doi: 10.1111/j.1365-2125.2004.02077.x.

Population pharmacokinetics of pyrimethamine and sulfadoxine in children with congenital toxoplasmosis

T Trenque  1 , N Simon, I Villena, C Chemla, C Quereux, B Leroux, R Jaussaud, G Rémy, D Dupouy, H Millart, J-M Pinon, S Urien
Affiliations

Population pharmacokinetics of pyrimethamine and sulfadoxine in children with congenital toxoplasmosis

T Trenque et al. Br J Clin Pharmacol. 2004 Jun.

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 chromatography. 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.

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Figures

Figure 1
Figure 1
Predicted (PRED) vs. observed (OBS) plasma pyrimethamine concentrations based on the basic, covariate-free, model (a) and the final pharmacokinetic model, including the effect of body weight on CL and V(b) (n = 89 children)
Figure 2
Figure 2
Predicted (PRED) vs. observed (OBS) plasma sulfadoxine concentrations based on the basic, covariate-free, model (a) and the final pharmacokinetic model, including the effect of body weight on CL and V(b) (n = 89 children)
Figure 3
Figure 3
Elimination half-lives of sulfadoxine (upper curve) and pyrimethamine (lower curve) as a function of body weight
See this image and copyright information in PMC

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