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Antimicrobial Agents and Chemotherapy, September 2005, p. 3658-3662, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3658-3662.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Quinine Pharmacokinetics and Pharmacodynamics in Children with Malaria Caused by Plasmodium falciparum

M. Le Jouan,1 V. Jullien,2 E. Tetanye,3 A. Tran,4 E. Rey,2 J.-M. Tréluyer,2 M. Tod,1* and G. Pons2

Department of Pharmacy-Toxicology,1 Department of Pharmacology, Hospital Cochin-Saint Vincent de Paul, AP-HP, René Descartes University, Paris, France,2 Department of Pediatrics, Hôpital Central, Biomedical Science Yaoundé University I, Yaoundé, Cameroon,3 Ecole Pratique des Hautes Etudes, Paris, France4

Received 24 February 2005/ Returned for modification 23 April 2005/ Accepted 4 June 2005

The aim of the present study was to assess the pharmacokinetics and the efficacy of a shorter than usual 5-day quinine treatment given orally to children in Cameroon with malaria caused by Plasmodium falciparum. Quinine (8.3 mg of base per kg of body weight every 8 h) was administered as a 2% formiate salt syrup for 5 days to 30 children (age range, 0.55 to 6.7 years) with uncomplicated falciparum malaria (initial parasitemia, 1.4 x 103 to 1.8 x 105/µl). Quinine concentrations in plasma samples (five to nine per patient) were measured by liquid chromatography on days 1 to 3. Parasitemia was counted on days 0, 1, 2, 3, 4, 7, and 14. Pharmacokinetic and pharmacodynamic data were analyzed by population approaches by using NONMEM and WinBugs, respectively. The kinetics of quinine were best described by a one-compartment model with time-varying protein binding. Clearance and the volume of distribution were positively correlated with body weight and increased over time. Parasitemia was undetectable from day 3 to 14 in all children. The time to a 4-log reduction of the initial level of parasitemia (Ter) was related to the average quinine concentration from 0 to 72 h (Cav) as Ter = Tmin [1 + (C50/Cav)s], where sigmoidicity (s) is equal to 2, Tmin is the time to eradication at infinite Cav, and C50 is the value of Cav for which Ter is twice Tmin. The C50 distribution was unimodal, and all C50 values were less than 8 mg/liter, while Cav ranged from 5.9 to 18.3 mg/liter. The median (10th to 90th percentile) Ter was 47 h (range, 39 to 76 h). The efficacy of a 5-day treatment course should be evaluated in a larger clinical trial.

* Corresponding author. Mailing address: Pharmacy, Cochin Hospital, 27 rue du Faubourg Saint-Jacques, Paris 75014, France. Phone: 33 1 58 41 23 13. Fax: 33 1 58 41 23 15. E-mail: michel.tod{at}cch.ap-hop-paris.fr.

Antimicrobial Agents and Chemotherapy, September 2005, p. 3658-3662, Vol. 49, No. 9
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.9.3658-3662.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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