An increase in urinary primaquine and a reduction in urinary primaquine-5,6-orthoquinone in the Thai population with CYP2D6 reduced enzyme function
Issued Date
2024-01-30
Resource Type
ISSN
24058440
Scopus ID
2-s2.0-85182586260
Journal Title
Heliyon
Volume
10
Issue
2
Rights Holder(s)
SCOPUS
Bibliographic Citation
Heliyon Vol.10 No.2 (2024)
Suggested Citation
Pookmanee W., Thongthip S., Mungthin M., Sukasem C., Tankanitlert J., Chariyavilaskul P., Wittayalertpanya S. An increase in urinary primaquine and a reduction in urinary primaquine-5,6-orthoquinone in the Thai population with CYP2D6 reduced enzyme function. Heliyon Vol.10 No.2 (2024). doi:10.1016/j.heliyon.2024.e24351 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/96008
Title
An increase in urinary primaquine and a reduction in urinary primaquine-5,6-orthoquinone in the Thai population with CYP2D6 reduced enzyme function
Corresponding Author(s)
Other Contributor(s)
Abstract
Objectives: Primaquine is metabolized by the cytochrome P450-2D6 enzyme (CYP2D6) to an active primaquine-5,6-orthoquinone (POQ). No relationships of CYP2D6 polymorphisms with the pharmacokinetics of primaquine and POQ were reported in the Thai population. Methods: We evaluated the genetic distribution of CYP2D6 in 345 Thai army populations together with the pharmacokinetic profiles of primaquine and POQ in plasma and urine (n = 44, descriptive data are presented in median (range)). All dose-related pharmacokinetic parameters were normalized by primaquine dose per body weight before statistical analysis. Results: CYP2D6*10 was the allele observed with the highest frequency (56.62%) corresponding to CYP2D6*10/*10 (32.94%) and CYP2D6*1/*10 (27.94%) genotypes. CYP2D6 intermediate metabolizers (CYP2D6 IM) were found in 44.41% of the cohort and had an increase in the cumulative amount of primaquine excreted (CAE) in urine compared to normal metabolizers of CYP2D6 (CYP2D6 NM); (CYP2D6 IM vs. CYP2D6 NM: 2444 (1697–3564) vs. 1757 (1092–2185) μg/mg/kg, p = 0.039), a reduction in urine CAE of POQ (CYP2D6 IM vs CYP2D6 NM: 115 (46–297) vs. 318 (92–498) μg/mg/kg, p = 0.047) and a reduction in the POQ/primaquine CAE ratio in urine (CYP2D6 IM vs. CYP2D6 NM: 0.06 (0.01–0.11) vs. 0.16 (0.06–0.26), p = 0.009). No significant differences were found in the pharmacokinetic profiles of plasma primaquine and POQ. Conclusions: The CYP2D6 polymorphisms influenced the changes in primaquine and POQ that were noticeable in the urine, supporting the role of the CYP2D6 gene testing before drug administration.