Pharmacokinetics of nicomorphine and its metabolites in man after epidural administration

Abstract

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.

Rectal administration of nicomorphine in patients improves biological availability of morphine and its glucuronide conjugates

“…Considering the fate of nicomorphine in the biological system and the apparent lack of intrinsic activities, the conclusion is justified that not the parent drug but rather the metabolites cause the drug to take effect in man. The serum concen tration-time course of nicomorphine and its metab olites depends on the route of administration, as shown earlier for the unconjugated compounds [4][5][6].…”

“…Blood samples of 5 ml were taken just before and at regular time intervals during and after anaesthesia: 1, 2, 3,4,5,6,7,8,10,15,20,30,45,60,90,120,240,360, 480 min, 12 h and 24 h after the adminis tration of nicomorphine. The samples were centri fuged at 3,000 rpm and the serum was stored at -20°C until analysis.…”

“…When given intravenously or intramuscularly, nico morphine is quickly metabolized to the metabolites 6MNM and morphine with a half-life of 1 min [5][6][7]. No 3MNM was detected.…”

“…In order to measure nicomorphine and its metab olites, we developed a sensitive method of analysis by means of high pressure liquid chromatography (HPLC) with electrochemical and UV detection [3], and described the pharmacokinetic behaviour of nicomorphine and its unconjugated metabolites 6-mononicotinoylmorphine (6MNM) and morphine [4][5][6]. Considering the fate of nicomorphine in the biological system and the apparent lack of intrinsic activities, the conclusion is justified that not the parent drug but rather the metabolites cause the drug to take effect in man.…”

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

“…Blood samples of 5 mL were taken just before and at regular time intervals during and after anaesthesia: 1, 2, 3,4, 5,6,7,8,10,15,20,30,45,60,90,120, and 240min after the administration of nicomorphine in patients 1-7. In patients 8-10, sampling was continued for a longer period: 6,8,12, and 24 h after the administration of nicomorphine.…”