Population pharmacokinetics of a three-day chloroquine treatment in patients with Plasmodium vivax infection on the Thai-Myanmar border

Malaria Journal

Research

Kesara Na-Bangchang¹  Anurak Cheomung¹  Ronnatrai Ruengweerayut²  Richard Höglund³  Angela Äbelö⁴  Younis Moussavi⁴ 

[1] Center of Excellence for Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, International College of Medicine, Thammasat University, Bangkok, Pathumtanee, Thailand;Mae Sot General Hospital, Mae Sot, Tak province, Thailand;Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand;Unit for Pharmacokinetics and Drug Metabolism, Department Pharmacology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden;

关键词: Plasmodium vivax;    Chloroquine;    Desethylchloroquine;    Population pharmacokinetics;    Drug resistance;   

DOI  :  10.1186/s12936-016-1181-1

 received in 2015-08-12, accepted in 2016-02-18,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundA three-day course of chloroquine remains a standard treatment of Plasmodium vivax infection in Thailand with satisfactory clinical efficacy and tolerability although a continuous decline in in vitro parasite sensitivity has been reported. Information on the pharmacokinetics of chloroquine and its active metabolite desethylchloroquine are required for optimization of treatment to attain therapeutic exposure and thus prevent drug resistance development.MethodsThe study was conducted at Mae Tao Clinic for migrant worker, Tak province, Thailand. Blood samples were collected from a total of 75 (8 Thais and 67 Burmeses; 36 males and 39 females; aged 17–52 years) patients with mono-infection with P. vivax malaria [median (95 % CI) admission parasitaemia 4898 (1206–29,480)/µL] following treatment with a three-day course of chloroquine (25 mg/kg body weight chloroquine phosphate over 3 days). Whole blood concentrations of chloroquine and desethylchloroquine were measured using high performance liquid chromatography with UV detection. Concentration–time profiles of both compounds were analysed using a population-based pharmacokinetic approach.ResultsAll patients showed satisfactory response to standard treatment with a three-day course of chloroquine with 100 % cure rate within the follow-up period of 42 days. Neither recurrence of P. vivax parasitaemia nor appearance of P. falciparum occurred. A total of 1045 observations from 75 participants were included in the pharmacokinetic analysis. Chloroquine disposition was most adequately described by the two-compartment model with one transit compartment absorption model into the central compartment and a first-order transformation of chloroquine into desethylchloroquine with an additional peripheral compartment added to desethylchloroquine. First-order elimination from the central compartment of chloroquine and desethylchloroquine was assumed. The model exhibited a strong predictive ability and the pharmacokinetic parameters were estimated with adequate precision.ConclusionThe developed population-based pharmacokinetic model could be applied for future prediction of optimal dosage regimen of chloroquine in patients with P. vivax infection.

【 授权许可】

CC BY   
© Höglund et al. 2016

【 图 表 】

Fig. 1