Impact of polymorphisms in CYP and UGT enzymes and ABC and SLCO1B1 transporters on the pharmacokinetics and safety of desvenlafaxine.
Article Details
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Calleja S, Zubiaur P, Ochoa D, Villapalos-Garcia G, Mejia-Abril G, Soria-Chacartegui P, Navares-Gomez M, de Miguel A, Roman M, Martin-Vilchez S, Abad-Santos F
Impact of polymorphisms in CYP and UGT enzymes and ABC and SLCO1B1 transporters on the pharmacokinetics and safety of desvenlafaxine.
Front Pharmacol. 2023 Feb 2;14:1110460. doi: 10.3389/fphar.2023.1110460. eCollection 2023.
- PubMed ID
- 36817149 [ View in PubMed]
- Abstract
Venlafaxine pharmacokinetic variability and pharmacotherapy outcomes are well known to be related to CYP2D6 pharmacogenetic phenotype. In contrast, scarce pharmacogenetic information is available nowadays concerning desvenlafaxine, its active metabolite first marketed in 2012. The aim of this study was to evaluate the impact of 29 alleles in 12 candidate genes (e.g., CYP enzymes like CYP2D6, CYP3A4, or CYP2C19; ABC transporters like ABCB1; SLCO1B1; and UGT enzymes like UGT1A1) on desvenlafaxine pharmacokinetic variability and tolerability. Pharmacokinetic parameters and adverse drug reaction (ADR) incidence obtained from six bioequivalence clinical trials (n = 98) evaluating desvenlafaxine formulations (five with single dose administration and one with multiple-dose administration) were analyzed. No genetic polymorphism was related to pharmacokinetic variability or ADR incidence. Volunteers enrolled in the multiple-dose clinical trial also showed a higher incidence of ADRs, e.g., xerostomia or appetite disorders. Volunteers experiencing any ADR showed a significantly higher area under the time-concentration curve (AUC) than those not experiencing any ADR (5115.35 vs. 4279.04 ng*h/mL, respectively, p = 0.034). In conclusion, the strong dose-dependent relationship with the occurrence of ADRs confirms that the mechanism of action of desvenlafaxine is essentially dose-dependent.
DrugBank Data that Cites this Article
- Drugs
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Desvenlafaxine Cytochrome P450 2C19 Protein Humans NoSubstrateDetails Desvenlafaxine Cytochrome P450 3A4 Protein Humans NoSubstrateInhibitorDetails Desvenlafaxine UDP-glucuronosyltransferase 1-1 Protein Humans NoSubstrateDetails Desvenlafaxine UDP-glucuronosyltransferase 1-3 Protein Humans NoSubstrateDetails Desvenlafaxine UDP-glucuronosyltransferase 2B15 Protein Humans NoSubstrateDetails Desvenlafaxine UDP-glucuronosyltransferase 2B17 Protein Humans NoSubstrateDetails Desvenlafaxine UDP-glucuronosyltransferase 2B4 Protein Humans NoSubstrateDetails - Drug Reactions
Reaction Details Details
