Rectal administration of nicomorphine in patients improves biological availability of morphine and its glucuronide conjugates.
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.
Koopman-Kimenai
P M
PM
Department of Clinical Pharmacy, Academic Hospital Nijmegen Sint Radboud, The Netherlands.
Vree
T B
TB
Booij
L H
LH
Dirksen
R
R
D000285:Administration, Rectal; D000328:Adult; D001682:Biological Availability; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008875:Middle Aged; D009020:Morphine / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics*; D009022:Morphine Derivatives / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D009539:Nicotinic Acids / Q000008:administration & dosage / Q000097:blood
D009022:Morphine Derivatives; D009539:Nicotinic Acids; C035349:morphine-6-glucuronide; D009020:Morphine; C018108:morphine-3-glucuronide; C008549:nicomorphine