Potential pharmacokinetic interactions of primaquine and blood chizontocides healthy thai volunteers
Issued Date
2014
Resource Type
Language
eng
Rights
Mahidol University
Suggested Citation
Borimas Hanboonkunupakarn, Podjanee Jittamala, พจนีย์ จิตตะมาลา, Tarning, Joel, Ashley, Elizabeth, Lee, Sue J, Salwaluk Panapipat, Nicholas Day, White, Nicholas J, Sasithon Pukrittayakamee, ศศิธร ผู้กฤตยาคามี (2014). Potential pharmacokinetic interactions of primaquine and blood chizontocides healthy thai volunteers. Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/63143
Title
Potential pharmacokinetic interactions of primaquine and blood chizontocides healthy thai volunteers
Abstract
Primaquine is a drug widely used with other schizontocides in treating
malaria. It has been used with chloroquine for radical treatment of vivax
malaria, and with artemisinin-based combination therapy (ACT) as a
gametocytocide to contain the spread of artemisinin-resistant Plasmodium falciparum.
Since primaquine and many other antimalarials are metabolized by cytochrome P450,
drug-drug interactions are likely to occur. We conducted 3 crossover studies in healthy
Thai adult volunteers to determine potential pharmacokinetic interactions between
primaquine and three other important blood schizontocides, namely chloroquine,
dihydroartemisinin-piperaquine, and pyronaridine-artesunate. In each study, all
volunteers were randomised into two groups of three sequential hospital admissions to
receive 30 mg base primaquine, the blood schizontocide under study (i.e., 600 mg base
chloroquine, 120-960 mg dihydroartemisinin-piperaquine or 540-180 mg pyronaridineartesunate)
and the combined drugs. The pharmacokinetic properties of all drugs were
evaluated using a non-compartmental approach. An analysis of variance (ANOVA)
was carried out on the log-transformed pharmacokinetic parameters for exposure to
assess the drug-drug interactions. All treatment regimens were well-tolerated and
none was associated with significant electrocardiographic QT prolongation. The single
oral dose of primaquine did not result in any significant pharmacokinetic alterations
of the studied schizontocides. In contrast, the co-administration with these long halflife
schizontocides significantly increased plasma primaquine concentrations. These
results suggest a synergistic effect of chloroquine and primaquine for curative treatment
in vivax malaria. They also confirm the recent WHO guideline that primaquine is to be
given in addition to ACT on the first day of treatment of falciparum malaria.
Description
Joint International Tropical Medicine Meeting 2014: 3D perspectives on tropical medicine: drivers, diversity and determination the 8th seminar on food-and water-borne parasitic zoonoses: 2-4 December 2014: Centara Grand Bangkok Convention Center at Central World, Bangkok, Thailand. Bangkok: Faculty of Tropical Medicine, Mahidol University; 2014. p. 232.