Article thumbnail
Location of Repository

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

By M. Le Jouan, V. Jullien, E. Tetanye, A. Tran, E. Rey, J.-M. Tréluyer, M. Tod and G. Pons

Abstract

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 × 10(3) to 1.8 × 10(5)/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 (T(er)) was related to the average quinine concentration from 0 to 72 h (C(av)) as T(er) = T(min) [1 + (C(50)/C(av))(s)], where sigmoidicity (s) is equal to 2, T(min) is the time to eradication at infinite C(av), and C(50) is the value of C(av) for which T(er) is twice T(min). The C(50) distribution was unimodal, and all C(50) values were less than 8 mg/liter, while C(av) ranged from 5.9 to 18.3 mg/liter. The median (10th to 90th percentile) T(er) was 47 h (range, 39 to 76 h). The efficacy of a 5-day treatment course should be evaluated in a larger clinical trial

Topics: Pharmacology
Publisher: American Society for Microbiology
Year: 2005
DOI identifier: 10.1128/AAC.49.9.3658-3662.2005
OAI identifier: oai:pubmedcentral.nih.gov:1195403
Provided by: PubMed Central
Download PDF:
Sorry, we are unable to provide the full text but you may find it at the following location(s):
  • http://dx.doi.org/10.1128/AAC.... (external link)
  • Suggested articles


    To submit an update or takedown request for this paper, please submit an Update/Correction/Removal Request.