RECTAL ADMINISTRATION OF NICOMORPHINE IN PATIENTS IMPROVES BIOLOGICALAVAILABILITY OF MORPHINE AND ITS GLUCURONIDE CONJUGATES

The pharmacokinetics of 30 mg nicomorphine after rectal administration with a suppository are described in 8 patients. under combined genera l and epidural anaesthesia. No nicomorphine or 6-mononicotinoylmorphin e could be detected in the serum. Morphine appeared almost instantaneo usly with a lag-time of 8 min and had a iinai elimination half-life of 1.48 +/- 0.48 h. Morphine was metabolized to morphine-3-glucuronide a nd morphine-6-glucuronide. These glucuronide conjugates appeared after a lag-time of 12 min and the half-life of these two glucuronide cojug ates was similar: about 2.8 h (P > 0.8). The glucuronide conjugate of 6-mononicotinoylmorphine was not detected. In the urine only morphine and its glucuronides were found. The renal clearance value for morphin e was 162 ml.min(-1) and for the glucuronides 81 ml.min(-1). This stud y shows that administration of a suppository with 30 mg nicomorphine g ives an excellent absolute bioavailability of morphine and its metabol ites of 88%. The lipid-soluble prodrug nicomorphine is quickly absorbe d and immediately hydrolysed to morphine.