No significant influence of OCT1 genotypes on the pharmacokinetics of morphine in adult surgical patients

Ida Kuhlmann, Rasmus Hjelmar Petersen, Morten Overgaard, Kenn Dornonville de la Cour, Stine Zwisler, Tore Bjerregaard Stage, Mette Marie Hougaard Christensen, Troels K Bergmann, Per Damkier, Anders Gadegaard Jensen, Flemming Nielsen, Kim Brøsen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

We investigated the impact of genetic variants in OCT1 (SLC22A1) on morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) pharmacokinetics in adult patients scheduled for major surgery. Blood samples were taken before and 5, 10, 15, 30, 45, 60 and 90 min after a bolus of morphine (0.15 mg/kg). Patients were genotyped for the genetic variants (rs12208357, rs34059508, rs72552763 and rs34130495) in OCT1. Eighty-six patients completed the trial. The mean difference (95% confidence interval) for dose adjusted morphine, M3G and M6G AUC was 0.9 (−0.7–2.4), −5.9 (−11.8 to −0.03) and −1.1 (−2.5–0.4) h/L*10 −6, respectively, in patients with two reduced function alleles compared to patients with no reduced function alleles in OCT1. Accordingly, the (AUC M3G/Dose)/(AUC morphine/Dose) and (AUC M6G/Dose)/(AUC morphine/Dose) ratio was reduced, −1.8 (−3.2 to −0.4) and −0.4 (−0.7 to −0.03), respectively, when comparing the same groups. OCT1 variants had no influence on the experience of pain, adverse events or the number of PCA doses used. In conclusion, genetic variants in OCT1 had a small and clinically unimportant impact on the exposure of morphine after intravenous administration. Our results do not support pre-emptive genotyping for OCT1 prior to morphine administration in patients scheduled for major surgery.

Original languageEnglish
Book seriesBasic & Clinical Pharmacology & Toxicology
Volume130
Issue number1
Pages (from-to)93-102
ISSN1742-7843
DOIs
Publication statusPublished - Jan 2022

Keywords

  • M6G
  • morphine
  • organic cation transporter 1
  • pharmacodynamics
  • pharmacokinetics

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