title: The bioavailability of intramuscularly administered nicomorphine (Vilan) with its metabolites and their glucuronide conjugates in surgical patients.
abstract: The kinetics of 20 mg nicomorphine intramuscularly were described in 8 patients under combined general and epidural anesthesia. The half-life of nicomorphine was 0.32 +/- 0.20 h (mean +/- SD) and is governed by the absorption-rather than the elimination rate. The half-life of 6-mononicotinoylmorphine (0.39 +/- 0.09 h) was identical to that of the parent compound (p = 0.29), suggesting it is directly related to the absorption rate of nicomorphine. Morphine had a half-life of 1.38 +/- 0.31 h. Morphine is subsequently metabolized into morphine-3-glucuronide and morphine-6-glucuronide. The half-life of these 2 glucuronide conjugates was about 2.6 h (p = 0.07). A glucuronide conjugate of 6-mononicotinoylmorphine was not detected. In urine only morphine and its glucuronides are found, with renal clearance values of 214 ml.min-1 for morphine and 132 ml.min-1 for the glucuronides. The bioavailability of this pharmaceutical formulation after intramuscular administration equals that of intravenous administration in surgical patients (at the same dose).
authors.affiliation: Department of Clinical Pharmacy, Academic Hospital Nijmegen Sint Radboud, 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: R
authors.initials: R
authors.lastname: Dirksen
mesh_terms: D000328:Adult; D001682:Biological Availability; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006801:Humans; D007273:Injections, Intramuscular; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009022:Morphine Derivatives / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D009539:Nicotinic Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000652:urine; D015203:Reproducibility of Results
chemical_list: D009022:Morphine Derivatives; D009539:Nicotinic Acids; C035349:morphine-6-glucuronide; C032054:morphine 6-nicotinate; D009020:Morphine; C053391:morphine 3-nicotinate; C018108:morphine-3-glucuronide; C008549:nicomorphine