Pupillometry in healthy volunteers as a biomarker of tramadol efficacy

J Clin Pharm Ther. 2011 Aug;36(4):513-7. doi: 10.1111/j.1365-2710.2010.01203.x. Epub 2010 Aug 24.


What is known and 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.

Results and discussion: 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.

What is new and conclusion: 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.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacokinetics
  • Analgesics, Opioid / pharmacology*
  • Biomarkers, Pharmacological / metabolism
  • Cytochrome P-450 CYP2D6 / genetics*
  • Cytochrome P-450 CYP2D6 / metabolism
  • Female
  • Humans
  • Male
  • Miosis / chemically induced
  • Mydriasis / chemically induced
  • Polymorphism, Genetic
  • Pupil / drug effects*
  • Tramadol / administration & dosage
  • Tramadol / pharmacokinetics
  • Tramadol / pharmacology*
  • Young Adult


  • Analgesics, Opioid
  • Biomarkers, Pharmacological
  • Tramadol
  • Cytochrome P-450 CYP2D6