Morphine and metabolite behavior after different routes of morphine administration: demonstration of the importance of the active metabolite morphine-6-glucuronide

Clin Pharmacol Ther. 1990 Jan;47(1):12-9. doi: 10.1038/clpt.1990.2.


The pharmacokinetic parameters of morphine, morphine-6-glucuronide, and morphine-3-glucuronide were studied after single-dose morphine administration by five different routes. The quantitative significance of the active metabolite morphine-6-glucuronide was assessed, and the effects of novel dosing forms on morphine metabolism and distribution were examined. After administration of intravenous morphine the morphine-6-glucuronide plasma AUC exceeded that of morphine. After administration of oral morphine very low morphine levels were observed--the morphine-6-glucuronide plasma AUC exceeded that of morphine by a factor of 9:1. Sublingual, buccal, and sustained-release buccal morphine tablet administration resulted in delayed absorption, with attenuation and delay of peak morphine and metabolite levels. Morphine bioavailability and morphine glucuronide production were not altered.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Adult
  • Delayed-Action Preparations
  • Half-Life
  • Humans
  • Injections, Intravenous
  • Metabolic Clearance Rate
  • Morphine / administration & dosage*
  • Morphine / blood
  • Morphine / pharmacokinetics
  • Morphine Derivatives / blood
  • Morphine Derivatives / metabolism*
  • Tablets


  • Delayed-Action Preparations
  • Morphine Derivatives
  • Tablets
  • morphine-6-glucuronide
  • Morphine
  • morphine-3-glucuronide