Population pharmacokinetics of pyrimethamine and sulfadoxine in children with congenital toxoplasmosis
| Autor: | B. Leroux, J. M. Pinon, R. Jaussaud, Saik Urien, Cathy Chemla, C. Quereux, Nicolas Simon, G. Remy, T. Trenque, Isabelle Villena, H. Millart, D. Dupouy |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Male
Adolescent Sulfadoxine medicine.medical_treatment Population Pharmacology Toxoplasmosis Congenital Folinic acid Pharmacokinetics medicine Humans Pharmacology (medical) education Child Chromatography High Pressure Liquid Antibacterial agent education.field_of_study medicine.diagnostic_test business.industry Infant Newborn Infant Confidence interval Drug Combinations Pyrimethamine Therapeutic drug monitoring Child Preschool Female business medicine.drug |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|