title: 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.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacy, Academic Hospital Nijmegen Sint Radboud, Geert Grooteplein Zuid 8, GA Nijmegen, The Netherlands.
authors.forename: P M
authors.initials: PM
authors.lastname: Koopman-Kimenai
authors.forename: T B
authors.initials: TB
authors.lastname: Vree
authors.forename: L H
authors.initials: LH
authors.lastname: Booij
authors.forename: M A
authors.initials: MA
authors.lastname: Hasenbos
mesh_terms: 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
chemical_list: D005965:Glucuronates; D009022:Morphine Derivatives; D009539:Nicotinic Acids; D009020:Morphine; C008549:nicomorphine