PHARMACOKINETICS OF EPIDURALLY ADMINISTERED NICOMORPHINE WITH ITS METABOLITES AND GLUCURONIDE CONJUGATES IN PATIENTS UNDERGOING PULMONARY SURGERY DURING COMBINED EPIDURAL LOCAL-ANESTHETIC BLOCK AND GENERAL-ANESTHESIA

After epidural administration of 15 mg 3, 6-dinicotinoylmorphine (nico morphine) in 10 patients undergoing pulmonary surgery, the parent comp ound was quickly metabolized into the metabolites 6-mononicotinoylmorp hine and morphine. The mean apparent half-lives (+/- SD) of eliminatio n 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 subsequentl y metabolized into morphine-3-glucuronide and morphine-6-glucuronide. The apparent half-lives of morphine, morphine-3-glucuronide, and morph ine-6-glucuronide are similar: 3.63 h +/- 1.63 h, 4.10 h +/- 0.57 h, a nd 4.20 h +/- 1.64 h respectively. The possible glucuronide conjugate of 6-mononicotinoylmorphine was not detected. The prodrug 3,6-dinicoti noylmorphine was biotransformed into three active compounds: 6-mononic otinoylmorphine, morphine, and morphine-6-glucuronide.