Abstract
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.
Highlights
A three-day course of chloroquine remains a standard treatment of Plasmodium vivax infection in Thailand with satisfactory clinical efficacy and tolerability a continuous decline in in vitro parasite sensitiv‐ ity has been reported
Apart from drug resistance in Plasmodium falciparum, the “sleeping giant” in the Greater Mekong subregion is P. vivax malaria, which has become resistant to the blood schizontocide chloroquine in some of the Southeast Asian countries, notably Indonesia [2, 3]
Patients were treated with the standard three-day chloroquine (Government Pharmaceutical Organization of Thailand, 250 mg chloroquine phosphate per tablet) regimen given at a total dose of 25 mg base/kg body weight over 3 days (10 and 5 mg/kg at 0 and 6–12 h on day 0, and 5 mg/kg each on day 1 and day 2) and primaquine (Government Pharmaceutical Organization of Thailand, 15 mg base per tablet) given at daily doses of 15 mg base/kg body weight daily for 14 days starting from the second day of chloroquine treatment
Summary
A three-day course of chloroquine remains a standard treatment of Plasmodium vivax infection in Thailand with satisfactory clinical efficacy and tolerability a continuous decline in in vitro parasite sensitiv‐ ity has been reported. Malaria remains one of the major global public health problems in the tropics and subtropics including Southeast Asia. Apart from drug resistance in Plasmodium falciparum, the “sleeping giant” in the Greater Mekong subregion is P. vivax malaria, which has become resistant to the blood schizontocide chloroquine in some of the Southeast Asian countries, notably Indonesia [2, 3]. The burden of P. vivax varies widely with the World Health Organization (WHO) estimating it being responsible for approximately 12–22 million cases worldwide annually [1]. The disease is rarely life-threatening, but morbidity from a prolonged illness and the possibility of relapses from a persistent hepatic form (hypnozoite) which occurs more frequently with the tropical form of P. vivax found in Southeast Asian countries, is of major concern and cause considerable economic loss
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