| Sažetak: | <strong>Background</strong>
Primaquine is the only widely available drug for radical cure of Plasmodium vivax malaria. There is uncertainty whether the pharmacokinetic properties of primaquine are altered significantly in childhood or not.
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<strong>Methods</strong>
Glucose-6-phosphate dehydrogenase normal patients with uncomplicated P. vivax malaria were randomized to receive either chloroquine (25mg base/kg) or dihydroartemisinin-piperaquine (dihydroartemisinin 7mg/kg and piperaquine 55mg/kg) plus primaquine; given either as 0.5 mg base/kg/day for 14 days or 1 mg/kg/day for 7 days. Pre-dose day 7 venous plasma concentrations of chloroquine, desethylchloroquine, piperaquine, primaquine and carboxyprimaquine were measured. Methemoglobin levels were measured on day 7.
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<strong>Results</strong>
Day 7 primaquine and carboxyprimaquine concentrations were available for 641 patients. After adjustment for the primaquine mg/kg daily dose, day of sampling, partner drug, and fever clearance, there was a significant non-linear relationship between age and trough primaquine and carboxyprimaquine concentrations, and day methemoglobin levels. Compared to adults 30 years of age, children 5 years of age had trough primaquine concentrations 0.53 (95% CI: 0.39- 0.73) fold lower, trough carboxyprimaquine concentrations 0.45 (95% CI: 0.35- 0.55) fold lower, and day 7 methemoglobin levels 0.87 (95% CI: 0.58-1.27) fold lower. Increasing concentrations of piperaquine and chloroquine and poor metabolizer CYP 2D6 alleles were associated with higher day 7 primaquine and carboxyprimaquine concentrations. Higher blood methemoglobin concentrations were associated with a lower risk of recurrence.
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<strong>Conclusion</strong>
Young children have lower primaquine and carboxyprimaquine exposures, and lower levels of methemoglobinemia, than adults. Young children may need higher weight adjusted primaquine doses than adults.
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