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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
Author(s) -
KoopmanKimenai Petronella M.,
Vree Tom B.,
Booij Leo H. D. J.,
Hasenbos Marcel A. W. M.
Publication year - 1995
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510160608
Subject(s) - morphine , glucuronide , pharmacokinetics , medicine , anesthesia , epidural administration , prodrug , conjugate , pharmacology , metabolite , chemistry , mathematical analysis , mathematics
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.