title: Population pharmacokinetics of a three-day chloroquine treatment in patients with Plasmodium vivax infection on the Thai-Myanmar border.
abstract: BACKGROUND
  A 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  All 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.
  
  
  CONCLUSIONS
  The developed population-based pharmacokinetic model could be applied for future prediction of optimal dosage regimen of chloroquine in patients with P. vivax infection.
authors.affiliation: Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand. Richard.H@tropmedres.ac.
authors.forename: Richard
authors.initials: R
authors.lastname: Höglund
authors.affiliation: Unit for Pharmacokinetics and Drug Metabolism, Department Pharmacology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. yonismoussawi@hotmail.com.
authors.forename: Younis
authors.initials: Y
authors.lastname: Moussavi
authors.affiliation: Mae Sot General Hospital, Mae Sot, Tak province, Thailand. ronnatrai@yahoo.com.
authors.forename: Ronnatrai
authors.initials: R
authors.lastname: Ruengweerayut
authors.affiliation: Center of Excellence for Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, International College of Medicine, Thammasat University, Bangkok, Pathumtanee, Thailand. anurak_ch9@yahoo.com.
authors.forename: Anurak
authors.initials: A
authors.lastname: Cheomung
authors.affiliation: Unit for Pharmacokinetics and Drug Metabolism, Department Pharmacology, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. angela.abelo@neuro.gu.se.
authors.forename: Angela
authors.initials: A
authors.lastname: Äbelö
authors.affiliation: Center of Excellence for Molecular Biology and Pharmacology of Malaria and Cholangiocarcinoma, International College of Medicine, Thammasat University, Bangkok, Pathumtanee, Thailand. kesaratmu@yahoo.com.
authors.forename: Kesara
authors.initials: K
authors.lastname: Na-Bangchang
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D002738:Chloroquine / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D004351:Drug Resistance; D005260:Female; D006801:Humans; D016780:Malaria, Vivax / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D008875:Middle Aged; D002052:Myanmar / Q000453:epidemiology; D010966:Plasmodium vivax / Q000187:drug effects*; D013785:Thailand / Q000453:epidemiology; D055815:Young Adult
chemical_list: D000962:Antimalarials; D002738:Chloroquine