Category Ranking
98%
Total Visits
921
Avg Visit Duration
2 minutes
Citations
20
Article Abstract
Objectives: Primaquine is metabolized by the cytochrome P450-2D6 enzyme (CYP2D6) to an active primaquine-5,6-orthoquinone (POQ). No relationships of polymorphisms with the pharmacokinetics of primaquine and POQ were reported in the Thai population.
Methods: We evaluated the genetic distribution of 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: was the allele observed with the highest frequency (56.62%) corresponding to (32.94%) and (27.94%) genotypes. intermediate metabolizers ( 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 ( NM); ( IM vs. NM: 2444 (1697-3564) vs. 1757 (1092-2185) μg/mg/kg, p = 0.039), a reduction in urine CAE of POQ ( IM vs 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 ( IM vs. 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 polymorphisms influenced the changes in primaquine and POQ that were noticeable in the urine, supporting the role of the gene testing before drug administration.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10827494 | PMC |
| http://dx.doi.org/10.1016/j.heliyon.2024.e24351 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Primaquine-5,6-Orthoquinone Is Directly Hemolytic to Older G6PD Deficient RBCs in a Humanized Mouse Model.
J Pharmacol Exp Ther
September 2024
Department of Pathology, University of Virginia School of Medicine, Charlottesville, Virginia (K.H.D.-C., A.M.H., J.C.Z.); Carter Immunology Center, University of Virginia, Charlottesville, Virginia (K.H.D.-C., A.M.H., J.C.Z.); Department of Biochemistry and Molecular Genetics, University of Colorad
Article Synopsis
- Primaquine and Tafenoquine are the only drugs that can cure malaria completely, but they pose risks for individuals with G6PD deficiency, potentially causing severe blood cell damage.
- The study introduces a new mouse model replicating a specific human G6PD variant, allowing researchers to observe how a metabolite called 5,6-POQ affects red blood cells.
- The research indicates that 5,6-POQ is not just a harmless byproduct of drug metabolism but actively contributes to the destruction of older red blood cells in G6PD-deficient individuals, challenging previous assumptions about its role.
An increase in urinary primaquine and a reduction in urinary primaquine-5,6-orthoquinone in the Thai population with CYP2D6 reduced enzyme function.
Heliyon
January 2024
Center of Excellence in Clinical Pharmacokinetics and Pharmacogenomics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Objectives: Primaquine is metabolized by the cytochrome P450-2D6 enzyme (CYP2D6) to an active primaquine-5,6-orthoquinone (POQ). No relationships of polymorphisms with the pharmacokinetics of primaquine and POQ were reported in the Thai population.
Methods: We evaluated the genetic distribution of 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)).
Quantitative determination of primaquine-5,6-ortho-quinone and carboxyprimaquine-5,6-ortho-quinone in human erythrocytes by UHPLC-MS/MS.
J Chromatogr B Analyt Technol Biomed Life Sci
January 2021
National Center for Natural Products Research, The University of Mississippi, University, MS 38677, USA. Electronic address:
The antimalarial drug primaquine (PQ) causes methemoglobinemia and hemolysis in individuals with a genetic deficiency of glucose 6-phosphate dehydrogenase. Reactive oxygen species (ROS) generated by redox cycling of the metabolite primaquine-5,6-orthoquinone (POQ) in erythrocytes has been attributed to be responsible for the toxicity of PQ. Carboxyprimaquine (CPQ), the major human plasma metabolite of PQ, can also form the analogous carboxyprimaquine-5,6-orthoquinone (CPOQ) metabolite, which can also generate ROS in erythrocytes by redox cycling, thus contributing to the hematotoxicity of this drug.
View Article and Find Full Text PDF