Explorative pharmacokinetic study of preoperative administration of morphine 50mg sustained-release capsules (Kapanol (TM)) to surgical patients

Objective: This study investigated the release, absorption and elimination profile of preoperatively administered sustained-release morphine (Kapanol( TM)) and its metabolites in patients undergoing surgery and general anaesth esia. Methods: Sustained-release morphine 50mg (37.6mg of morphine base) was admi nistered 1 to 2 hours before induction of anaesthesia in 10 patients underg oing elective surgery. Results: Mean plasma concentration-time curves showed a time to peak concen tration (t(max)) of 8.4 +/- 6.5 hours for morphine and 10.4 +/- 10.3 hours for both morphine-6-glucuronide (M6G) and morphine-3-glucuronide (M3G). The absorption half-life of morphine was 5.7 +/- 6.9 hours. The ratio of the a reas under the concentration-time curves for morphine, M6G and M3G was 1 : 3.5 : 28. The elimination half-lives of morphine and its metabolites were n ot significantly different at 15.0 +/- 8.95 hours. Conclusions: After preoperative oral administration, sustained-release morp hine 50mg was absorbed perioperatively in all 10 patients studied. The mean plasma concentration-time curve for morphine resembled that in healthy (no nsurgical) adult males receiving a single dose, and the concentrations atta ined would be expected to provide postoperative analgesia.