Does gender, food or grapefruit juice alter the pharmacokinetics of primaquine in healthy subjects?
OBJECTIVE
To evaluate the effects of gender, food and grapefruit juice on the pharmacokinetics of primaquine in healthy subjects.


METHODS
In a randomized, two-phase cross-over study, 10 male and 10 female healthy Vietnamese subjects were administered 30 mg primaquine in the fasting state or with food, followed by administration of primaquine with grapefruit juice.


RESULTS
The pharmacokinetics of primaquine were comparable between male and female subjects, with geometric mean ratios of Cmax = 0.89 [95% confidence interval (CI) 0.65, 1.22] and AUC = 0.80 (95% CI 0.56, 1.15). The mean CL/F of primaquine was slightly higher in males than in females [0.52 l h(-1) kg(-1)vs. 0.43 l h(-1) kg(-1), mean difference of 0.09 (95% CI -0.10, 0.28), P = 0.32]. When compared with fasting state values, food increased the geometric mean Cmax of primaquine by 26% (95% CI 12, 40) and the AUC by 14% (95% CI 3, 27). Similarly, grapefruit juice increased the geometric mean Cmax by 23% (95% CI 4, 45) and the AUC by 19% (95% CI 4, 37).


CONCLUSIONS
The disposition of primaquine was comparable between genders, suggesting no need to modify the dose of primaquine for malaria treatment or prophylaxis. Food increased the oral bioavailability of primaquine, which may lead to higher antimalarial efficacy. Grapefruit juice increased the bioavailability of primaquine, with marked interindividual differences suggesting that people should not take primaquine with grapefruit juice.
Cuong
Bui Tri
BT
Department of Infectious Disease, Central Military Hospital, Hanoi, Vietnam.
Binh
Vu Quoc
VQ
Dai
Bui
B
Duy
Dinh Ngoc
DN
Lovell
Claire M
CM
Rieckmann
Karl H
KH
Edstein
Michael D
MD
D000328:Adult; D000962:Antimalarials / Q000493:pharmacokinetics*; D001628:Beverages; D032083:Citrus paradisi; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D011319:Primaquine / Q000493:pharmacokinetics*; D012727:Sex Characteristics
D000962:Antimalarials; D011319:Primaquine