Pharmacokinetics of epidurally administered nicomorphine with its metabolites and glucuronide conjugates in patients undergoing pulmonary surgery during combined epidural local anaesthetic block and general anaesthesia.
After epidural administration of 15 mg 3, 6-dinicotinoylmorphine (nicomorphine) in 10 patients undergoing pulmonary surgery, the parent compound was quickly metabolized into the metabolites 6-mononicotinoylmorphine and morphine. The mean apparent half-lives (+/- SD) of elimination were 10 min (0.165 h +/- 0.053 h) for 3,6-dinicotinoylmorphine and 1.77 h +/- 1.23 h for 6-mononicotinoylmorphine. Morphine is subsequently metabolized into morphine-3-glucuronide and morphine-6-glucuronide. The apparent half-lives of morphine, morphine-3-glucuronide, and morphine-6-glucuronide are similar: 3.63 h +/- 1.63 h, 4.10 h +/- 0.57 h, and 4.20 h +/- 1.64 h respectively. The possible glucuronide conjugate of 6-mononicotinoylmorphine was not detected. The prodrug 3,6-dinicotinoylmorphine was biotransformed into three active compounds: 6-mononicotinoylmorphine, morphine, and morphine-6-glucuronide.
Koopman-Kimenai
P M
PM
Department of Clinical Pharmacy, Academic Hospital Nijmegen Sint Radboud, Geert Grooteplein Zuid 8, GA Nijmegen, The Netherlands.
Vree
T B
TB
Booij
L H
LH
Hasenbos
M A
MA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000767:Anesthesia, Epidural; D000768:Anesthesia, General; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005965:Glucuronates / Q000097:blood / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D008168:Lung / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000097:blood; D009022:Morphine Derivatives / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009539:Nicotinic Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D013056:Spectrophotometry, Ultraviolet
D005965:Glucuronates; D009022:Morphine Derivatives; D009539:Nicotinic Acids; D009020:Morphine; C008549:nicomorphine