Aim: Metoprolol (a CYP2D6 substrate) is often co-prescribed with paroxetine/fluoxetine (a CYP2D6 inhibitor) because the clinical relevance of this drug-drug interaction (DDI) is still unclear. This review aimed to systematically evaluate the available evidence and quantify the clinical impact of the DDI.

These DDI predictions may explain the occurrence of severe sinus bradycardia after coadministration of bupropion and metoprolol and highlight the need for caution and dosage adjustment when combining bupropion with medications metabolized by CYP2D6.

The cytochrome P450 (CYP) 2D6 enzyme is particularly prone to DDGIs due to the high prevalence of genetic variation and common use of CYP2D6 inhibiting drugs. In this study, we present a comprehensive PBPK network covering CYP2D6 drug …

The aim of this study was to quantitatively explain the in vivo CYP2D6 DDI magnitude by in vitro DDI data. Bupropion and its metabolites were found to inhibit CYP2D6 stereoselectively with up to 10-fold difference in inhibition potency between enantiomers.

Feb 14, 2025 · In this study, we present a comprehensive PBPK network covering CYP2D6 drug–gene interactions (DGIs), DDIs, and DDGIs. The network covers sensitive and moderate sensitive substrates, and strong and weak inhibitors of CYP2D6 according to the United States Food and Drug Administration (FDA) guidance.

Cytochrome P450 family 2 subfamily D member 6 (CYP2D6) contributes to 2% and 0.7% of the overall hepatic and intestinal cytochrome P450 enzyme, respectively, and is estimated to be responsible for metabolism of 25% of commonly prescribed drugs (e.g., antidepressants, antipsychotics, opioids, beta blockers). Significant interpatient variability ...

Feb 26, 2024 · In vitro time-dependent inhibition (TDI) kinetic parameters for cytochrome P450 (CYP) 1A2, 2B6, 2C8, 2C9, 2C19, and 2D6, were determined in pooled human liver microsomes for 19 drugs (and 2 metabolites) for which clinical drug-drug interactions (DDI) are known.

Sep 24, 2018 · Metoprolol (a CYP2D6 substrate) is often co-prescribed with paroxetine/fluoxetine (a CYP2D6 inhibitor) because the clinical relevance of this drug–drug interaction (DDI) is still unclear. This review aimed to systematically evaluate the available evidence and quantify the clinical impact of the DDI.

Jan 1, 2021 · CYP screening showed that CYP3A4, 1A2, and 2D6 were the three most significant isoenzymes contributing to erlotinib metabolism. With fluoxetine’s known potent (strong) CYP2D6 and mild/moderate CYP3A4 inhibition, assays were designed to investigate DDIs between erlotinib and fluoxetine in terms of CYP2D6 and 3A4.

The in vivo sensitivities of the clinically relevant CYP2D6 substrates desipramine, dextromethorphan, and metoprolol were determined on the basis of literature drug-drug interaction (DDI) outcomes. Similar to the in vitro results, dextromethorphan exhibited the highest sensitivity to CYP2D6 inhibition in vivo.