title: Tramadol efficacy in patients with postoperative pain in relation to CYP2D6 and MDR1 polymorphisms.
abstract: OBJECTIVE
  The aim of our study was to evaluate impact of CYP2D6 and MDR1 polymorphisms on the analgesic efficacy of tramadol in patients after a knee arthroscopy.
  
  
  BACKGROUND
  Pharmacokinetics of tramadol and its metabolites is stereoselective and displays high interindividual variability correlating with polymorphic CYP2D6 in the population. Available data provide controversial results regarding the analgesic efficacy of tramadol in subjects with different CYP2D6 genotypes.
  
  
  METHODS
  Pain intensity was assessed using visual analogue scale at 2 and 24 hours after the knee arthroscopy in 156 patients. Polymorphisms CYP2D6*3,*4,*5,*6, and gene duplication and C3435T in MDR1 gene were analyzed by PCR - RFLP.
  
  
  RESULTS
  Mean VAS2h value in the whole study group was 44.0 ± 16.5 mm. Mean pain difference, was lowest in the UM group and highest in the PM group. The pain difference varied significantly among the CYP2D6 subgroups (F = 4.29; p = 0.006) with significant differences between homEM vs hetEM, homEM vs PM, and UM vs PM subgroups. There were no significant differences among MDR1 subgroups with regards of pain difference. Mean tramadol consumption was 2.47 ± 1.17 mg/kg during the 24 h period. There were no significant differences in the drug consumption, reporting of adverse reactions, need for rescue analgesic medication or verbal description of pain among the CYP2D6 or MDR1 genotype subgroups.
  
  
  CONCLUSIONS
  CYP2D6 plays a significant role in tramadol analgesic efficacy. The non-opioid analgesia in PMs was associated with better subjective pain relief in patients after a knee arthroscopy (Tab. 3, Ref. 18).
authors.affiliation: Charles University, Prague, Czech Republic. oslan@lf1.cuni.cz
authors.forename: O
authors.initials: O
authors.lastname: Slanar
authors.forename: P
authors.initials: P
authors.lastname: Dupal
authors.forename: O
authors.initials: O
authors.lastname: Matouskova
authors.forename: H
authors.initials: H
authors.lastname: Vondrackova
authors.forename: P
authors.initials: P
authors.lastname: Pafko
authors.forename: F
authors.initials: F
authors.lastname: Perlik
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D001182:Arthroscopy; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D007719:Knee Joint / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D011110:Polymorphism, Genetic; D014147:Tramadol / Q000627:therapeutic use*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000701:Analgesics, Opioid; D014147:Tramadol; D019389:Cytochrome P-450 CYP2D6