Vivax malaria: preliminary observations following a shorter course of treatment with artesunate plus primaquine.

The standard adult treatment regimen for Plasmodium vivax malaria is chloroquine (1500 mg over 3 d) plus primaquine (15 or 30 mg daily for 14 d), but patient compliance tends to be poor with the lengthy course. Preliminary observations are reported on the efficacy of a shorter treatment course - artesunate (200mg twice a day for 2 d) plus primaquine (22.5mg base twice a day for 7 d) - given to 28 adult patients infected with P. vivax in Viet Nam. All patients responded quickly to treatment with mean (SD) parasite and fever clearance times of 14.2 (4.0) and 18.6 (8.4) h, respectively. The high dose of primaquine was generally well tolerated, and only one patient (3.6%) had a recurrence of parasitaemia during 28 d of follow-up. As most patients infected with Southeast Asian strains of P. vivax have their first relapse within 28 d after treatment with rapidly eliminated blood schizonticides, the absence of parasitaemia in the remaining 27 patients suggests that this drug regimen was active against both blood and liver stages. Further studies are needed to confirm that this rapidly acting, short artesunate-primaquine regimen can result in better patient compliance and treatment outcomes than the chloroquine-primaquine regimen.

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 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.