Population Pharmacokinetics of Primaquine in the Korean Population
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 clinica...
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| Format: | Article |
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MDPI AG
2021-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/13/5/652 |
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| author | Woo-Yul Lee Dong-Woo Chae Choon-Ok Kim Sang-Eun Lee Yee-Gyung Kwak Joon-Sup Yeom Kyung-Soo Park |
| author_facet | Woo-Yul Lee Dong-Woo Chae Choon-Ok Kim Sang-Eun Lee Yee-Gyung Kwak Joon-Sup Yeom Kyung-Soo Park |
| author_sort | Woo-Yul Lee |
| collection | DOAJ |
| description | 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 (<i>p</i> < 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. |
| first_indexed | 2024-03-10T11:43:00Z |
| format | Article |
| id | doaj.art-094c9b55a3d24a519b2353496986d49c |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T11:43:00Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-094c9b55a3d24a519b2353496986d49c2023-11-21T18:16:51ZengMDPI AGPharmaceutics1999-49232021-05-0113565210.3390/pharmaceutics13050652Population Pharmacokinetics of Primaquine in the Korean PopulationWoo-Yul Lee0Dong-Woo Chae1Choon-Ok Kim2Sang-Eun Lee3Yee-Gyung Kwak4Joon-Sup Yeom5Kyung-Soo Park6Department of Pharmacology, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment of Pharmacology, Yonsei University College of Medicine, Seoul 03722, KoreaClinical Trials Center, Severance Hospital, Yonsei University Health System, Seoul 03722, KoreaKorea Centers for Disease Control and Prevention, Cheongju 28159, KoreaDepartment of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang 10380, KoreaDepartment of Internal Medicine, Yonsei University College of Medicine, Seoul 03722, KoreaDepartment of Pharmacology, Yonsei University College of Medicine, Seoul 03722, KoreaWhile 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 (<i>p</i> < 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.https://www.mdpi.com/1999-4923/13/5/652primaquinepharmacokineticsCYP2D6carboxy-primaquinemalariapopulation pharmacokinetics |
| spellingShingle | Woo-Yul Lee Dong-Woo Chae Choon-Ok Kim Sang-Eun Lee Yee-Gyung Kwak Joon-Sup Yeom Kyung-Soo Park Population Pharmacokinetics of Primaquine in the Korean Population Pharmaceutics primaquine pharmacokinetics CYP2D6 carboxy-primaquine malaria population pharmacokinetics |
| title | Population Pharmacokinetics of Primaquine in the Korean Population |
| title_full | Population Pharmacokinetics of Primaquine in the Korean Population |
| title_fullStr | Population Pharmacokinetics of Primaquine in the Korean Population |
| title_full_unstemmed | Population Pharmacokinetics of Primaquine in the Korean Population |
| title_short | Population Pharmacokinetics of Primaquine in the Korean Population |
| title_sort | population pharmacokinetics of primaquine in the korean population |
| topic | primaquine pharmacokinetics CYP2D6 carboxy-primaquine malaria population pharmacokinetics |
| url | https://www.mdpi.com/1999-4923/13/5/652 |
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