Population pharmacokinetics of amodiaquine and piperaquine in African pregnant women with uncomplicated Plasmodium falciparum infections
1
Issued Date
2024-01-01
Resource Type
eISSN
21638306
Scopus ID
2-s2.0-85203188526
Journal Title
CPT: Pharmacometrics and Systems Pharmacology
Rights Holder(s)
SCOPUS
Bibliographic Citation
CPT: Pharmacometrics and Systems Pharmacology (2024)
Suggested Citation
Ding J., Hoglund R.M., Tagbor H., Tinto H., Valéa I., Mwapasa V., Kalilani-Phiri L., Van Geertruyden J.P., Nambozi M., Mulenga M., Hachizovu S., Ravinetto R., D'Alessandro U., Tarning J. Population pharmacokinetics of amodiaquine and piperaquine in African pregnant women with uncomplicated Plasmodium falciparum infections. CPT: Pharmacometrics and Systems Pharmacology (2024). doi:10.1002/psp4.13211 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/101194
Title
Population pharmacokinetics of amodiaquine and piperaquine in African pregnant women with uncomplicated Plasmodium falciparum infections
Author's Affiliation
WorldWide Antimalarial Resistance Network
Kamuzu University of Health Sciences
Mahidol Oxford Tropical Medicine Research Unit
University of Health and Allied Sciences, Ghana
Tropical Diseases Research Centre Ndola
University of the Western Cape
London School of Hygiene & Tropical Medicine
Prins Leopold Instituut voor Tropische Geneeskunde
Universiteit Antwerpen
Nuffield Department of Medicine
Clinical Research Unit of Nanoro
Kamuzu University of Health Sciences
Mahidol Oxford Tropical Medicine Research Unit
University of Health and Allied Sciences, Ghana
Tropical Diseases Research Centre Ndola
University of the Western Cape
London School of Hygiene & Tropical Medicine
Prins Leopold Instituut voor Tropische Geneeskunde
Universiteit Antwerpen
Nuffield Department of Medicine
Clinical Research Unit of Nanoro
Corresponding Author(s)
Other Contributor(s)
Abstract
Artemisinin-based combination therapy (ACT) is the first-line recommended treatment for uncomplicated malaria. Pharmacokinetic (PK) properties in pregnant women are often based on small studies and need to be confirmed and validated in larger pregnant patient populations. This study aimed to evaluate the PK properties of amodiaquine and its active metabolite, desethylamodiaquine, and piperaquine in women in their second and third trimester of pregnancy with uncomplicated P. falciparum infections. Eligible pregnant women received either artesunate-amodiaquine (200/540 mg daily, n = 771) or dihydroartemisinin-piperaquine (40/960 mg daily, n = 755) for 3 days (NCT00852423). Population PK properties were evaluated using nonlinear mixed-effects modeling, and effect of gestational age and trimester was evaluated as covariates. 1071 amodiaquine and 1087 desethylamodiaquine plasma concentrations, and 976 piperaquine plasma concentrations, were included in the population PK analysis. Amodiaquine concentrations were described accurately with a one-compartment disposition model followed by a two-compartment disposition model of desethylamodiaquine. The relative bioavailability of amodiaquine increased with gestational age (1.25% per week). The predicted exposure to desethylamodiaquine was 2.8%–32.2% higher in pregnant women than that reported in non-pregnant women, while day 7 concentrations were comparable. Piperaquine concentrations were adequately described by a three-compartment disposition model. Neither gestational age nor trimester had significant impact on the PK of piperaquine. The predicted exposure and day 7 concentrations of piperaquine were similar to that reported in non-pregnant women. In conclusion, the exposure to desethylamodiaquine and piperaquine was similar to that in non-pregnant women. Dose adjustment is not warranted for women in their second and their trimester of pregnancy.