Cristin-resultat-ID: 1873056
Sist endret: 10. februar 2021, 10:54
NVI-rapporteringsår: 2020
Resultat
Vitenskapelig artikkel
2020

Impact of genotype-predicted CYP2D6 metabolism on clinical effects and tolerability of metoprolol in patients after myocardial infarction – a prospective observational study

Bidragsytere:
  • Anne Kristine Anstensrud
  • Espen Molden
  • Hans Jørgen Haug
  • Rehman Ul-Haq Qazi
  • Hysen Muriq
  • Linn Elisabeth Lillerud Fosshaug
  • mfl.

Tidsskrift

European Journal of Clinical Pharmacology
ISSN 0031-6970
e-ISSN 1432-1041
NVI-nivå 2

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2020
Volum: 76
Sider: 673 - 683
Open Access

Importkilder

Scopus-ID: 2-s2.0-85078610925

Beskrivelse Beskrivelse

Tittel

Impact of genotype-predicted CYP2D6 metabolism on clinical effects and tolerability of metoprolol in patients after myocardial infarction – a prospective observational study

Sammendrag

Purpose The β-1 adrenergic receptor blocker metoprolol is primarily metabolized by the polymorphic enzyme cytochrome P 450 2D6 (CYP2D6), an enzyme with substantial genetic heterogeneity. Our purpose was to investigate the impact of CYP2D6 metabolism on clinical effects and tolerability of metoprolol in patients after myocardial infarction (MI). Methods We included 136 patients with MI discharged on treatment with metoprolol with a recommendation to the general practitioner (GP) to increase the metoprolol dose up to 200 mg/day within 2 months if possible. At follow-up, metoprolol dosage after up-titration, metoprolol steady-state trough plasma concentrations, hemodynamic parameters, potential metoprolol-induced adverse drug reactions and number of visits to the GP were measured. CYP2D6 genotyping including the reduced-function variant alleles CYP2D6*9, CYP2D6*10 and CYP2D6*41 was performed after end of follow-up. Results According to the genotype-defined CYP2D6 phenotypes, 30% of the patients were metoprolol extensive metabolizers (EMs), 55% intermediate metabolizers (IMs) and 13% poor metabolizers (PMs; carriers of non-coding and reduced-function variant included). Dose-adjusted metoprolol trough concentrations were significantly higher in IM (2-fold) and PM (6.2-fold) groups vs. the EM group (p  6-fold increase of dose-adjusted plasma metoprolol trough concentration in CYP2D6 PMs vs. EMs with a parallel lower increase in achieved maximum HR during exercise but without association between genotype and frequency or severity of self-reported adverse drug effects. This may indicate that CYP2D6 PMs potentially could benefit of the increased plasma concentration per dose in a naturalistic setting.

Bidragsytere

Anne Kristine Anstensrud

  • Tilknyttet:
    Forfatter
    ved Klinikk for medisin ved Diakonhjemmet sykehus

Espen Molden

  • Tilknyttet:
    Forfatter
    ved Senter for Psykofarmakologi ved Diakonhjemmet sykehus
  • Tilknyttet:
    Forfatter
    ved Farmasøytisk institutt ved Universitetet i Oslo

Hans Jørgen Haug

  • Tilknyttet:
    Forfatter
    ved Hjertemedisinsk avdeling ved Universitetet i Oslo

Rehman Ul-Haq Qazi

  • Tilknyttet:
    Forfatter
    ved Klinikk for medisin ved Diakonhjemmet sykehus

Hysen Muriq

  • Tilknyttet:
    Forfatter
    ved Klinikk for medisin ved Diakonhjemmet sykehus
1 - 5 av 8 | Neste | Siste »