OPEN Research Support
head

PhD Student
Ida Robertsdottor Berglund Kuhlmann
Department of Clinical Biochemistry and Pharmacology, Odense University Hospital


Projekt styring
Projekt status    Planning
 
Data indsamlingsdatoer
Start 01.03.2017  
Slut 31.03.2021  
 



Inter- og intraindividuelle variationer i metformins farmakokinetik - betydning af gener og lægemiddelinteraktioner

Short summary

we will examine the effect of gene variants in the Organic Cation Transporter 1 (encoded by the SLC22A1 gene also known as OCT1) on the systemic exposure of morphine in a cohort of patients undergoing planned colon or rectum surgery receiving intravenous (iv) morphine during and after the operation. We will also study the impact of OCT1 pharmacogenetics on the total selfadministered dose of morphine, time to first self-administered dose as well as the analgesic response and adverse drug effects.


Rationale

Morphine exists in it´s protonated, i.e. cationic, form at physiologic pH, and is therefore transported across cell membranes by cation transporters. The OCT1 transporter is located on the sinusoidal membrane of hepatocytes, and it transports morphine into the hepatocytes where it is glucuronidated to the active metabolites morphine-6-glucuronide (M6G) and inactive metabolite M3G.

 The study is based on the hypothesis that morphine given intravenously is metabolized more slowly in patients with one or two loss-of-function alleles (v) in the OCT1 due to slow transport into the liver compared with patients with two wild-type (wt) alleles. We also hypothesize that patients with the v/v or v/wt genotypes require lower self-administered doses of morphine and experience a longer time before the first self-administered dose of morphine is needed in order to avoid pain, but do not suffer from less adverse effects than wt/wt patients.


Description of the cohort

90 patients undergoing planned colon or rectum surgery at Odense University hospital or South-West Jutland Hospital. 


Data and biological material

Data: concentrations of morphine and its metabolites; OCT1 status. Pain at rest and during activity, opioid side effects and level of sedation will be registered at regular time intervals. The total use and time interval for morphine dosing will be registered.

Biological material: blood


Collaborating researchers and departments

Clinical Pharmacology and Pharmaceutics, University of Southern Denmark

  • Professor Kim Brøsen, MD, DMSc
  • Postdoc Tore Stage, MSc, PhD

Department of Clinical Biochemistry and Pharmacology, Odense University Hospital

  • Professor Per Damkier, MD, PhD
  • Mette Marie Christensen, MD, PhD
  • Troels Bergman, MD, PhD

Department of Anaesthesiology, Odense University hospital

  • Stine Thorhauge Zwisler, MD, PhD

Department of Anaesthesiology, South-West Jutland Hospital.

  • Rasmus Hjelmar Petersen, MD
  • Morten Overgaard, MD