Rectal administration of nicomorphine in patients improves biological availability of morphine and its glucuronide conjugates

Pharm World Sci. 1994 Dec 2;16(6):248-53. doi: 10.1007/BF02178565.

Abstract

The pharmacokinetics of 30 mg nicomorphine after rectal administration with a suppository are described in 8 patients under combined general and epidural anaesthesia. No nicomorphine or 6-mononicotinoylmorphine could be detected in the serum. Morphine appeared almost instantaneously with a lag-time of 8 min and had a final elimination half-life of 1.48 +/- 0.48 h. Morphine was metabolized to morphine-3-glucuronide and morphine-6-glucuronide. These glucuronide conjugates appeared after a lag-time of 12 min and the half-life of these two glucuronide conjugates was similar: about 2.8 h (P > 0.8). The glucuronide conjugate of 6-mononicotinoylmorphine was not detected. In the urine only morphine and its glucuronides were found. The renal clearance value for morphine was 162 ml.min-1 and for the glucuronides 81 ml.min-1. This study shows that administration of a suppository with 30 mg nicomorphine gives an excellent absolute bioavailability of morphine and its metabolites of 88%. The lipid-soluble prodrug nicomorphine is quickly absorbed and immediately hydrolysed to morphine.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Rectal
  • Adult
  • Biological Availability
  • Drug Interactions
  • Female
  • Half-Life
  • Humans
  • Injections, Intravenous
  • Kidney / metabolism
  • Middle Aged
  • Morphine / blood
  • Morphine / metabolism
  • Morphine / pharmacokinetics*
  • Morphine Derivatives / administration & dosage*
  • Morphine Derivatives / blood
  • Morphine Derivatives / pharmacokinetics*
  • Nicotinic Acids / administration & dosage
  • Nicotinic Acids / blood

Substances

  • Morphine Derivatives
  • Nicotinic Acids
  • morphine-6-glucuronide
  • Morphine
  • morphine-3-glucuronide
  • nicomorphine