Evaluation of pharmacokinetics of single-dose primaquine in undernourished versus normally nourished children diagnosed with Plasmodium vivax malaria in Mumbai

Abstract

Background: The pharmacokinetics of primaquine [PQ] have been the subject of studies in both adults and healthy participants. However, there is no study on its pharmacokinetics in a setting of undernourishment. In India, there is evidence to show considerable malnourishment in children that in turn can affect drug pharmacokinetics. Given that the country is moving towards malaria elimination, the present study was planned with the objective of comparing pharmacokinetics of the drug in undernourished children relative to normally nourished children. Materials and Methods: After Institutional Ethics Committee approval, children of either gender between the ages of 5 and 12 years and smear-positive for Plasmodium vivax malaria were included. Nourishment status was determined using the Indian Academy of Pediatrics classification of protein energy malnutrition based on Khadilkar's growth charts. Twelve children each were enrolled in the two groups. PQ was given in the dose of 0.3 mg/kg/d and blood collections were made at 0, 1, 2, 3, 4, 6, 8 and 24 hours post-dosing. Levels were estimated by high-performance liquid chromatography. Chloroquine in the dose of 25 mg/kg was given over three days along with supportive care. Results: Of the 24 children, there were 17 boys and 7 girls. There was a statistically significant difference in the body weight between the undernourished and the normally nourished children [21.5 ± 5.52 vs. 28.8 ± 8.84, P < 0.05]. PQ levels showed wide inter-individual variation in both groups. No significant difference was seen in any pharmacokinetic parameter between the two groups. Discussion: This study adds to the limited body of evidence on the pharmacokinetics of PQ in children with malaria and indicates that the dosing of primaquine could potentially be independent of the nourishment status.