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Dexketoprofen Pharmacokinetics is not Significantly Altered by Genetic Polymorphism
Gina Mejía-Abril1,2, Pablo Zubiaur1,2, Marcos Navares-Gómez1
1Clinical Pharmacology Department, Hospital Universitario de La Princesa, Instituto Teófilo Hernando, Universidad Autónoma de Madrid (UAM), Instituto de Investigación Sanitaria La Princesa (IP), Madrid, Spain.
Frontiers in Pharmacology
|May 17, 2021
Summary
This study explored dexketoprofen pharmacogenetics, finding sex and specific gene polymorphisms (CYP1A2, CYP2B6, CYP2D6, ABCB1) influence drug pharmacokinetics. However, current evidence doesn't support routine genetic testing for dexketoprofen dosing adjustments.
Area of Science:
- Pharmacogenetics
- Clinical Pharmacology
- Drug Metabolism
Background:
- Dexketoprofen, an NSAID, is the active enantiomer of ketoprofen.
- No prior studies have investigated the pharmacogenetics of dexketoprofen.
- Understanding genetic influences is crucial for optimizing drug therapy.
Purpose of the Study:
- To investigate the impact of sex, race, and single nucleotide polymorphisms (SNPs) in metabolizing enzyme and transporter genes on dexketoprofen pharmacokinetics and safety.
- To determine if genetic polymorphisms could guide dexketoprofen dosing adjustments.
Main Methods:
- Genotyping of 46 SNPs across 14 genes in 85 healthy volunteers from bioequivalence trials.
- Analysis of pharmacokinetic parameters (AUC/DW, Vd/F, Cl/F, Cmax/DW) in relation to genetic variations and sex.
- Statistical analysis including univariate and multivariate approaches.
Main Results:
- Women exhibited different pharmacokinetic profiles (lower AUC/DW, higher Vd/F, Cl/F) compared to men.
- Specific alleles/phenotypes of CYP1A2, CYP2B6, CYP2D6, and ABCB1 were associated with variations in drug accumulation and peak concentration.
- No significant associations were found for other studied genes (ABCC2, SLC22A1, SLCO1B1, CYP3A5, CYP2C19, CYP2C9, CYP2C8, CYP3A4, CYP2A6, UGT1A1).
Conclusions:
- Dexketoprofen pharmacokinetics are influenced by sex and specific genetic polymorphisms in CYP and ABCB1 genes.
- No single pharmacogenetic marker is currently sufficient to warrant individualized dexketoprofen therapy.
- Further research is needed to validate the role of identified SNPs in CYP1A2, CYP2B6, CYP2D6, and ABCB1 for dexketoprofen pharmacokinetics.
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