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PHC-015 Impact of MDR1 Polymorphisms on the Analgesic Efficacy of Tramadol in Patients After Minor Surgery
  1. H. Bakhouche1,
  2. O Matouskova2,
  3. O Polanecky3,
  4. J Adamkova3,
  5. S Adamek3,
  6. O Slanar4
  1. 1General Teaching Hospital Charles University in Prague (Vseobecná fakultní nemocnice), Hospital pharmacy, Prague, Czech Republic
  2. 2First Faculty of Medicine and General Teaching Hospital Charles University in Prague, Institute of Pharmacology, Prague, Czech Republic
  3. 3First Faculty of Medicine and University Hospital Motol Charles University in Prague, Third Department of Surgery, Prague, Czech Republic
  4. 4First Faculty of Medicine and General Teaching Hospital Charles University in Prague, Institute of Pharmacology, Prague, Czech Republic

Abstract

Background P-glycoprotein is a transmembrane transporter coded by the ATP-binding cassette sub-family B multi-drug resistance gene (MDR-1) gene. It influences the bioavailability, disposition and excretion of many drugs. Among the 50 SNPs of the MDR1 gene, more attention has been focused on the SNP at position 3435 in exon 26. Homozygous TT samples were associated with more than two-fold lower intestinal MDR1 expression levels compared with homozygous CC samples. A trial in patients suffering from chronic and cancer pain reported decreased opioid consumption in carriers of the 3435T allele. Our previous data suggest that the pharmacokinetics and therefore effectiveness of tramadol could be affected by MDR1 polymorphism C3435T.

Purpose To evaluate the possible effect of MDR1 polymorphisms on the analgesic efficacy of tramadol in realistic clinical settings.

Materials and Methods Pain intensity was assessed using a visual analogue scale at 2 and 24 hours after minor surgery in 156 patients. Polymorphisms and gene duplication in the MDR1 gene were analysed by PCR–RFLP (restriction fragment length polymorphism).

Results Variant allele 3435T was seen at a frequency of 58.3%. There were no statistically significant differences between MDR1 subgroups in basic demographic parameters. Mean VAS2h in groups C3435CC, C3435CT and C3435TT were 40.0 ± 11.8; 43.2 ± 17.9, resp. 45.5 ± 16.1 mm (P = ns). Corresponding values for mean pain difference, defined as VAS2–24h were 19.3 ± 12.1; 21.3 ± 14.6 and 23.4 ± 15.4 mm (P = ns). Mean tramadol consumption was 2.47 ± 1.17, resp. 2.62 ± 1.1; 2.42 ± 1.1; 2.44 ± 1.3 mg/kg (P = ns) during the 24 h period. There were no significant differences in the drug consumption, reporting of adverse reactions or need for rescue analgesics among the MDR1 genotype subgroups.

Conclusions Although there were approximately 20% higher mean pain difference values in the 3435TT group in comparison with the wild-type subjects, the between-group variation did not reach statistical significance.

No conflict of interest.

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