morphine-6-nicotinate and nicomorphine

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).

Topics: Adult; Biological Availability; Calibration; Chromatography, High Pressure Liquid; Female; Half-Life; Humans; Injections, Intramuscular; Middle Aged; Morphine; Morphine Derivatives; Nicotinic Acids; Reproducibility of Results

Intravenous doses of 30, 20 and 10 mg nicomorphine (Vilan) are extremely quickly metabolized into the metabolites 6-nicotinoylmorphine and morphine. The half-lives of elimination are respectively 3 min for nicomorphine, 3 and 15 min for 6-nicotinoylmorphine, and 135-190 min for morphine. The kinetics of the 30 and 20 mg dose are comparable, the 10 mg dose shows patient dependent variations in metabolism. The AUC of the parent drug and its metabolites is linearly related to the dose.

Topics: Adult; Anesthesia, Epidural; Anesthesia, Intravenous; Bupivacaine; Female; Half-Life; Humans; Injections, Intravenous; Metabolic Clearance Rate; Middle Aged; Morphine; Morphine Derivatives; Nicotinic Acids; Preanesthetic Medication; Thiopental

In ten patients who received an epidural injection of 15 mg of nicomorphine, the compound was relatively slowly released from the epidural space and was found in plasma for approximately 1.5 h. Nicomorphine is relatively slowly metabolized into 6-nicotinoylmorphine and morphine. The rate of release is patient-dependent. The relative AUC values are 15.3% for nicomorphine, 23.9% for 6-nicotinoylmorphine and 60.8% for morphine. The mean clinical effect lasts for 18.2 +/- 10.1 h.

Topics: Adolescent; Adult; Aged; Analgesia, Epidural; Female; Half-Life; Humans; Injections, Epidural; Male; Middle Aged; Morphine; Morphine Derivatives; Nicotinic Acids

After i.m. injection nicomorphine is relatively slowly absorbed from the muscular depot and is found in the serum for approximately 1 h. The rate of absorption differs between patients and governs the overall pharmacokinetic profile of the compound. The relative AUCs were nicomorphine 18%, 6-nicotinoylmorphine 17%, and morphine 65%. Nicomorphine and 6-nicotinoylmorphine have significantly higher AUCs after i.m. injection than after i.v. injection, while the AUC of morphine and the total AUC show no difference between the two modes of administration.

Topics: Adult; Female; Half-Life; Humans; Injections, Intramuscular; Middle Aged; Morphine; Morphine Derivatives; Nicotinic Acids; Premedication; Time Factors

Morphine and its nicotinoyl esters, dinicotinoylmorphine (nicomorphine), 6-mononicotinoylmorphine (6-MNM) and 3-mononicotinoylmorphine (3-MNM) were tested in mice for central activity to obtain time-effect profiles of these compounds in rats. Two effects, analgesia with the hot plate test and locomotor stimulation in activity cages were measured and nicomorphine, 6-MNM and 3-MNM were found to have a faster onset of action compared with morphine. The effects of 3-MNM and morphine lasted longer than the effect of nicomorphine and 6-MNM. The prodrug behaviour of 3-MNM and nicomorphine for morphine and 6-MNM, respectively, is discussed.

Topics: Animals; Male; Mice; Morphine Derivatives; Motor Activity; Nicotinic Acids; Pharmaceutical Preparations; Prodrugs; Reaction Time

Topics: Biotransformation; Chromatography, High Pressure Liquid; Humans; Kinetics; Morphine; Morphine Derivatives; Nicotinic Acids; Spectrophotometry, Ultraviolet