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Aim: Nicomorphine is rapidly metabolized mainly to the biologically active 6-nicotinoyl morphine and morphine. In sport, morphine and nicomorphine use is prohibited whereas codeine use is permitted. Accredited laboratories routinely test for morphine hence must be able to distinguish morphine, as a metabolite of a prohibited substance, from that whose use is permitted. Results: Here we show a relatively simple method to synthesize the nicomorphine metabolites, 3-nicotinoyl and 6-nicotinoyl morphine, and indicate how they may be used to identify nicomorphine administration. Conclusion: This approach should help confirm that it is not codeine, an allowable analgesic in sport, that has been administered.

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.

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.

Es wird der Metabolismus von Nicomorphin (Morphin-3,6-dinicotinat, MDN) im Blut und Hirn von Ratten untersucht. Im Hirn und im Blut sind vorwiegend die Hydrolyseprodukte von MDN, das Morphin-6-nicotinat (MMN) sowie freies Morphin (M) nachzuweisen. Sie stellen somit die eigentlichen Wirkformen des Nicomorphins dar. Fur Vollblut und Gesamthirn erreicht man nach Applikation von 14C markiertem MDN mittels der analytischen Kombinationsmethode von Extraktion aus der biologischen Matrix und anschliesende HPLC-Auftrennung sowie Fraktionssammlung der identifizierten MDN, MMN und M Peakvolumina und deren quantitative off-line Radioaktivitatsmessung Nachweisgrenzen von 1 ppb. Pharmacokinetics of Nicomorphine in Rats HPLC Separation and Off-Line Scintillation Counting of Metabolites The metabolism and the pharmacokinetics of 14C-Nicomorphine (morphine 3,6-dinicotinate, MDN) were studied in female rats. Following i.v. administration MDN rapidly crosses the blood-brain barrier and is hydrolysed mainly to morphine 6-nicotinate (MMN), which is the main pharmacologically effective form of MDN. Morphine 6-nicotinate is deacylated to free morphine (M) which is another pharmacologically active metabolite of MDN. By HPLC separation of the blood and brain extracts, collection of the fractions containing MDN, MMN and M and off-line scintillation counting of these fractions we were able to achieve detection limits of one ppb for MDN, MMN and M.

A patient with severe bullous emphysema in whom one bulla occupied more than 25% of the hemithorax, with a shift of the mediastinum to the opposite side, was anaesthetised for bullectomy with a combination of intravenous gamma-hydroxybutyric acid and a high thoracic extradural catheter technique. During the operation the patient breathed 100% oxygen through a double-lumen endobronchial tube in the lateral thoracotomy position. Extradural analgesia during the operation was provided by bupivacaine 0.25%, with adrenaline 1:200 000 and, postoperatively, with nicomorphine diluted in dextrose 5%. The advantages of this technique are described.

• The electrical activity of the stomach and intestine was monitored during the postoperative period in 30 patients who underwent cholecystectomy. All patients received standard general anesthesia with artificial ventilation during operation; some received high epidural analgesia during surgery and postoperatively, and others, fentanyl analgesia during surgery and nicomorphine afterwards. Electroenterography EEnG showed that electrical activity decreased following surgery and returned to base line on the third or fourth day after operation. A marked increase in amplitude and frequency of EEnG oscillations was recorded in 80% of the patients who received bupivacaine injections into the epidural space. A decrease was almost always recorded after nicomorphine injections. During the postoperative period, eating caused a considerable increase in the amplitude and frequency of the electrical activity of the stomach and intestine in patients treated by epidural analgesia, whereas no observable change was recorded in patients treated by nicomorphine injections. It appears that high epidural analgesia may be useful in the treatment of postoperative adynamic ileus. ( Arch Surg 112:580-583, 1977)