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Population Pharmacokinetics of Primaquine in the Korean Population

 Woo-Yul Lee  ;  Dong-Woo Chae  ;  Choon-Ok Kim  ;  Sang-Eun Lee  ;  Yee-Gyung Kwak  ;  Joon-Sup Yeom  ;  Kyung-Soo Park 
 PHARMACEUTICS, Vol.13(5) : 652, 2021-05 
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CYP2D6 ; carboxy-primaquine ; malaria ; pharmacokinetics ; population pharmacokinetics ; primaquine
While primaquine has long been used for malaria treatment, treatment failure is common. This study aims to develop a population pharmacokinetic model of primaquine and its metabolite, carboxyprimaquine, and examine factors influencing pharmacokinetic variability. The data was obtained from a clinical study in 24 Korean subjects randomly assigned to normal and obese groups. The participants received primaquine 15 mg daily for 4 days and blood samples were collected at day 4. Pharmacokinetic modeling was performed with NONMEM and using simulations; the influences of doses and covariates on drug exposure were examined. A minimal physiology-based pharmacokinetic model connected with a liver compartment comprehensively described the data, with CYP450 mediated clearance being positively correlated with the body weight and CYP2D6 activity score (p < 0.05). In the simulation, while the weight-normalized area under drug concentration for primaquine in the obese group decreased by 29% at the current recommended dose of 15 mg, it became similar to the normal weight group at a weight-normalized dose of 3.5 mg/kg. This study has demonstrated that the body weight and CYP2D6 activity score significantly influence the pharmacokinetics of primaquine. The developed model is expected to be used as a basis for optimal malaria treatment in Korean patients.
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6. Others (기타) > Dept. of Clinical Pharmacology (임상시험센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Choon Ok(김춘옥) ORCID logo
Park, Kyungsoo(박경수) ORCID logo
Yeom, Joon Sup(염준섭) ORCID logo
Chae, Dong Woo(채동우) ORCID logo
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