title: Pupillometry in healthy volunteers as a biomarker of tramadol efficacy.
abstract: OBJECTIVE
  The opioid effect of tramadol, which can be detected by pupillary response, is predominantly mediated by the O-demethylated metabolite, formed via CYP2D6. This study was designed to evaluate the effects of tramadol using different parameters of pupillometry as biomarkers.
  
  
  METHODS
  Sixty-nine healthy volunteers received tramadol hydrochloride drops orally at a dose of 0·7 mg/kg. Pre-dose and 2-h post-dose pupillometric measurements were performed. The polymorphism of CYP2D6 was analysed.
  
  
  CONCLUSIONS
  Large interindividual variability was observed in the tramadol-induced pupillary reaction. Miosis was induced in 69·6% and mydriasis in 30·4% of the subjects. The pupillary response differed in relation to the CYP2D6 genotype. A maximal difference in initial pupil diameter of 0·81 mm was found in extensive metabolizers. There were significant effects observed on the pupillary light reflex parameters with tramadol administration (P < 0·05) except for the reflex amplitude and constriction velocity.
  
  
  CONCLUSIONS
  The pharmacodynamic effects of tramadol were easily detected using both static and dynamic pupil parameters. The pharmacodynamic profiles were markedly influenced by the CYP2D6 phenotype.
authors: Clinical Pharmacology Unit, Institute of Pharmacology, 1st Faculty of Medicine, Charles University, Prague, Czech Republic.
authors: O
authors: O
authors: Matouskova
authors: O
authors: O
authors: Slanar
authors: L
authors: L
authors: Chytil
authors: F
authors: F
authors: Perlik
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D015877:Miosis / Q000139:chemically induced; D015878:Mydriasis / Q000139:chemically induced; D011110:Polymorphism, Genetic; D011680:Pupil / Q000187:drug effects*; D014147:Tramadol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000701:Analgesics, Opioid; D054316:Biomarkers, Pharmacological; D014147:Tramadol; D019389:Cytochrome P-450 CYP2D6