Disposition in humans of racemic picenadol, an opioid analgesic

P. M. Franz, S. L. Anliker, J. T. Callaghan, K. A. DeSante, P. H. Dhahir, R. L. Nelson, A. Rubin

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Abstract

Racemic picenadol is being tested clinically as a analgesic. The (+)-enantiomer of picenadol is an opioid agonist and the (-)-enantiomer is a weak agonist/antagonist. The disposition of racemic [14C]picenadol was studied in healthy men after a single dose was administered im (N = 3) and orally (N = 5). After the dose, virtually none of the radioactivitiy that appeared in blood was associated with the red cells. In plasma, approximately 4% of the radioactivity was attributable to the parent drug, the remainder being picenadol glucuronide (~35%) and other metabolites. The t( 1/2 ) for total radioactivity was 6 hr, that for the unchanged drug was 3.5 hr. Picenadol was present in plasma almost exclusively as the (+)-enantiomer. However, after incubation with glucuronidase and sulfatase, plasma contained 2 to 4 times more (-)- than (+)-picenadol, indicating that more conjugated (-)-picenadol than conjugated (+)-picenadol was in the plasma. After im and oral administration of [14C]picenadol, plasma levels of radioactivity were generally 10 and 70 times higher than those in saliva, respectively. More than 90% of the administered radioactivity was excreted in the urine, mostly as picenadol glucuronide, and lesser amounts of picenadol sulfate and N-desmethylpicenadol sulfate. Only about 1% of the administered dose of picenadol appeared unchanged in urine. The disposition of racemic picenadol in humans was stereoselective, the (-)-picenadol apparently being metabolized preferentially over the (+)-enantiomer. This finding was of particular interest in view of the dissimilar pharmacologic activities of the enantiomers. In a separate multiple dose study of picenadol, the disposition of the drug was found to be similar to that in the single dose study.

Original languageEnglish (US)
Pages (from-to)968-973
Number of pages6
JournalDrug Metabolism and Disposition
Volume18
Issue number6
StatePublished - Dec 1 1990

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ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Franz, P. M., Anliker, S. L., Callaghan, J. T., DeSante, K. A., Dhahir, P. H., Nelson, R. L., & Rubin, A. (1990). Disposition in humans of racemic picenadol, an opioid analgesic. Drug Metabolism and Disposition, 18(6), 968-973.