Population Pharmacokinetics of Chloroquine in Malaria: A Prior Model in P. vivax Patients.

Chloroquine remains the standard treatment for p. vivax infections in Thailand, showing good effectiveness and tolerability. Understanding the pharmacokinetics of chloroquine and its metabolite is crucial for optimizing treatment and preventing drug resistance. This study is aimed toevaluate the pharmacokinetic and pharmacodynamic properties of chloroquine and its active metabolite, desethylchloroquine, in patients with p. vivax malaria. Whole blood samples were collected from 68 patients with p. vivax malaria in Northwestern Thailand. All patients received a standard three-day treatment of chloroquine (10+10+5 mg/kg chloroquine base). Parent and metabolite drug concentrations were quantified in the collected samples and parasite clearance were determined. Due to sparseness of the pharmacokinetic data, an informative prior from an unpublished study of chloroquine and desethylchloroquine in healthy volunteers was utilized. All data analysis were performed in NONMEM v7.5. In the prior model, chloroquine was described by a three-compartment disposition model with two transit absorption compartments, and the metabolite, desethylchloroquine, was described using a two-compartment model. The applied prior approach described the observed data well. Individually derived concentration-time profiles were used to describe the relationship between antimalarial drug exposure and parasite clearance rate.