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Quine pharmacokinetics and pharmacodynamics in children with falciparum malaria
Author(s) -
Le Jouan M.,
Jullien V.,
Tetanye Ekoe E.,
Tran A.,
Rey E.,
Treluyer J.,
Tod M.,
Pons G.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.11.071
Subject(s) - parasitemia , pharmacokinetics , nonmem , pharmacodynamics , volume of distribution , medicine , pharmacology , population , dosing , plasmodium falciparum , malaria , immunology , environmental health
Purpose To assess the pharmacokinetics, efficacy and safety of quinine (Quin) as an oral formulation in children with falciparum (fal) malaria following W.H.O. dosing recommendations. Methods Quin (8.3 mg/kg base every 8h) was administered as a 2 % formiate salt syrup during 5 days to 30 children (0.5 ‐ 6y.) from Cameroun with uncomplicated fal malaria (parasitemia 10 3 to 2.10 5 /μL). Quin concentration was measured in plasma samples (5 to 8 / patient) at day 1 ‐ 3 by HPLC. Parasitemia was counted at day 0, 1, 2, 3, 4, 7 and 14. Data were analyzed by parametric and non‐parametric population approaches (NONMEM and WINBUGS). Results Quin was well tolerated and parasitemia was null at day 4, 7 and 14 in all children. Quin kinetics was best described by a one‐compartment model with time‐varying protein binding. Clearance and distribution volume were positively correlated with body weight and increased over time. Median (range) AUC 0–72 h was 606 (422 ‐ 1316) h.mg/L. The time to 99.99 % reduction of parasitemia was related to Quin 0–72h average concentration Cav as: T= Tmin[1+ (EC 50 /Cav) s ] with sigmoidicity s= 2. The median (interindividual CV) minimal time Tmin was 35h (40%). EC 50 distribution was unimodal with median: 4.9 mg/L and 90 th percentile: 9 mg/L. Conclusions Oral Quin (8.3 mg/kg tid for 5d) was efficient and safe for treating children with fal malaria. Eradication was obtained in 96h at most. The model suggests a therapeutic range for Cav greater than 9 mg/L. Clinical Pharmacology & Therapeutics (2005) 77 , P18–P18; doi: 10.1016/j.clpt.2004.11.071