Population pharmacokinetics of primaquine and its metabolites in African males
Issued Date
2024-12-01
Resource Type
eISSN
14752875
Scopus ID
2-s2.0-85193603437
Journal Title
Malaria Journal
Volume
23
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Malaria Journal Vol.23 No.1 (2024)
Suggested Citation
Chotsiri P., Mahamar A., Diawara H., Fasinu P.S., Diarra K., Sanogo K., Bousema T., Walker L.A., Brown J.M., Dicko A., Gosling R., Chen I., Tarning J. Population pharmacokinetics of primaquine and its metabolites in African males. Malaria Journal Vol.23 No.1 (2024). doi:10.1186/s12936-024-04979-y Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/98493
Title
Population pharmacokinetics of primaquine and its metabolites in African males
Author's Affiliation
Université des Sciences, des Techniques et des Technologies de Bamako
Mahidol Oxford Tropical Medicine Research Unit
UCSF School of Medicine
London School of Hygiene & Tropical Medicine
The University of Alabama at Birmingham
University of California, San Francisco
University of Mississippi School of Pharmacy
Nuffield Department of Medicine
Radboud University Medical Center
Mahidol Oxford Tropical Medicine Research Unit
UCSF School of Medicine
London School of Hygiene & Tropical Medicine
The University of Alabama at Birmingham
University of California, San Francisco
University of Mississippi School of Pharmacy
Nuffield Department of Medicine
Radboud University Medical Center
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: Primaquine (PQ) is the prototype 8-aminoquinoline drug, a class which targets gametocytes and hypnozoites. The World Health Organization (WHO) recommends adding a single low dose of primaquine to the standard artemisinin-based combination therapy (ACT) in order to block malaria transmission in regions with low malaria transmission. However, the haemolytic toxicity is a major adverse outcome of primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient subjects. This study aimed to characterize the pharmacokinetic properties of primaquine and its major metabolites in G6PD-deficient subjects. Methods: A single low-dose of primaquine (0.4–0.5 mg/kg) was administered in twenty-eight African males. Venous and capillary plasma were sampled up to 24 h after the drug administration. Haemoglobin levels were observed up to 28 days after drug administration. Only PQ, carboxy-primaquine (CPQ), and primaquine carbamoyl-glucuronide (PQCG) were present in plasma samples and measured using liquid chromatography mass spectrometry. Drug and metabolites’ pharmacokinetic properties were investigated using nonlinear mixed-effects modelling. Results: Population pharmacokinetic properties of PQ, CPQ, and PQCG can be described by one-compartment disposition kinetics with a transit-absorption model. Body weight was implemented as an allometric function on the clearance and volume parameters for all compounds. None of the covariates significantly affected the pharmacokinetic parameters. No significant correlations were detected between the exposures of the measured compounds and the change in haemoglobin or methaemoglobin levels. There was no significant haemoglobin drop in the G6PD-deficient patients after administration of a single low dose of PQ. Conclusions: A single low-dose of PQ was haematologically safe in this population of G6PD-normal and G6PD-deficient African males without malaria. Trial registration NCT02535767