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An increase in urinary primaquine and a reduction in urinary primaquine-5,6-orthoquinone in the Thai population with CYP2D6 reduced enzyme function.
Pookmanee, Waritda; Thongthip, Siriwan; Mungthin, Mathirut; Sukasem, Chonlaphat; Tankanitlert, Jeeranut; Chariyavilaskul, Pajaree; Wittayalertpanya, Supeecha.
Afiliación
  • Pookmanee W; Interdisciplinary Program in Pharmacology, Graduate School, Chulalongkorn University, Bangkok, Thailand.
  • Thongthip S; Center of Excellence in Clinical Pharmacokinetics and Pharmacogenomics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Mungthin M; Medical Depot Division, Royal Thai Army Medical Department, Bangkok, Thailand.
  • Sukasem C; Maha Chakri Sirindhorn Clinical Research Center under the Royal Patronage, Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Tankanitlert J; Department of Pharmacology, Phramongkutklao College of Medicine, Bangkok, Thailand.
  • Chariyavilaskul P; Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
  • Wittayalertpanya S; Laboratory for Pharmacogenomics, Somdech Phra Debaratana Medical Center, Ramathibodi Hospital, Bangkok, Thailand.
Heliyon ; 10(2): e24351, 2024 Jan 30.
Article en En | MEDLINE | ID: mdl-38293439
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Heliyon Año: 2024 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Heliyon Año: 2024 Tipo del documento: Article País de afiliación: Tailandia Pais de publicación: Reino Unido