Background and Objectives: The primary objective was to compare the serum pharmacokinetic profile of a single dose of extended-release epidural morphine (EREM) administered alone versus 15 to 60 mins after an analgesic epidural dose of bupivacaine.

Methods: This multicenter study enrolled 144 patients, 18 years or older, with scheduled lower abdominal surgery under general anesthesia. Patients were randomly assigned to a single 15-mg dose of EREM; the same dose administered 15, 30, or 60 mins after epidural bupivacaine (20 mL 0.25%); or epidural placebo (normal saline) administered 15, 30, or 60 mins after bupivacaine. Postoperatively, fentanyl patient-controlled analgesia was offered for breakthrough pain. Multiple serum samples were analyzed for morphine and morphine metabolites. Safety and efficacy were assessed.

Results: The mean maximum serum concentration and area under the concentration-time curve for morphine and metabolites were not significantly different when EREM was administered alone versus 15, 30, or 60 mins after bupivacaine. Median time to maximum serum concentration and median apparent terminal elimination half-life were also comparable. Total fentanyl patient-controlled analgesia consumption was comparable among all EREM groups (with/without prior bupivacaine) but significantly (P < 0.05) lower compared with the bupivacaine + placebo group. Nausea, vomiting, and dizziness were consistently more frequent in groups receiving EREM after bupivacaine versus EREM alone.

Conclusions: The pharmacokinetic and efficacy profiles of a single 15-mg dose of EREM were not significantly altered when administered 15, 30, or 60 mins after an analgesic epidural dose of bupivacaine.