Does gender, food or grapefruit juice alter the pharmacokinetics of primaquine in healthy subjects?

Aims 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 C-max = 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 C-max of primaquine by 26% (95% CI 12, 40) and the AUC by 14% (95% CI 3, 27). Similarly, grapefruit juice increased the geometric mean C-max 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.