Mechanistic Modeling of Primaquine Pharmacokinetics, Gametocytocidal Activity, and Mosquito Infectivity
Issued Date
2022-03-01
Resource Type
ISSN
00099236
eISSN
15326535
DOI
Scopus ID
2-s2.0-85123474502
Pubmed ID
34905220
Journal Title
Clinical Pharmacology and Therapeutics
Volume
111
Issue
3
Start Page
676
End Page
685
Rights Holder(s)
SCOPUS
Bibliographic Citation
Clinical Pharmacology and Therapeutics Vol.111 No.3 (2022) , 676-685
Suggested Citation
Chotsiri P., Mahamar A., Hoglund R.M., Koita F., Sanogo K., Diawara H., Dicko A., Simpson J.A., Bousema T., White N.J., Brown J.M., Gosling R., Chen I., Tarning J. Mechanistic Modeling of Primaquine Pharmacokinetics, Gametocytocidal Activity, and Mosquito Infectivity. Clinical Pharmacology and Therapeutics Vol.111 No.3 (2022) , 676-685. 685. doi:10.1002/cpt.2512 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/86084
Title
Mechanistic Modeling of Primaquine Pharmacokinetics, Gametocytocidal Activity, and Mosquito Infectivity
Other Contributor(s)
Abstract
Clinical studies have shown that adding a single 0.25 mg base/kg dose of primaquine to standard antimalarial regimens rapidly sterilizes Plasmodium falciparum gametocytes. However, the mechanism of action and overall impact on malaria transmission is still unknown. Using data from 81 adult Malians with P. falciparum gametocytemia who received the standard dihydroartemisinin-piperaquine treatment course and were randomized to receive either a single dose of primaquine between 0.0625 and 0.5 mg base/kg or placebo, we characterized the pharmacokinetic-pharmacodynamic relationships for transmission blocking activity. Both gametocyte clearance and mosquito infectivity were assessed. A mechanistically linked pharmacokinetic-pharmacodynamic model adequately described primaquine and carboxy-primaquine pharmacokinetics, gametocyte dynamics, and mosquito infectivity at different clinical doses of primaquine. Primaquine showed a dose-dependent gametocytocidal effect that precedes clearance. A single low dose of primaquine (0.25 mg/kg) rapidly prevented P. falciparum transmissibility.