Pharmacokinetics of extended-release epidural morphine sulfate: pooled analysis of six clinical studies.

Author(s): Viscusi ER, Gambling DR, Hughes TL, Manvelian GZ

Affiliation(s): Department of Anesthesiology, Jefferson Medical College, Thomas Jefferson University, 111 South 11th Street, Philadelphia, PA 19107, USA. eugene.viscusi@jefferson.edu

Publication date & source: 2009-06-01, Am J Health Syst Pharm., 66(11):1020-30.

Publication type: Comparative Study; Meta-Analysis

PURPOSE: A pooled analysis of six clinical studies was conducted to describe the pharmacokinetics of extended-release epidural morphine sulfate. METHODS: Data from six clinical studies evaluating extended-release epidural morphine sulfate in volunteers and abdominal or hip surgery patients were pooled and analyzed. Participants age 18 years or older received extended-release epidural morphine sulfate (2.5-40 mg) within 30 minutes of surgery initiation. Most participants received a test dose of 1.5% lidocaine with 1:200,000 epinephrine for epidural space identification 15 minutes before study drug administration. Blood samples were generally collected at 0.5, 2, 4, 8, 12, 18, 24, and 48 hours postinjection. RESULTS: Standard epidural morphine sulfate exhibited a spike in drug release, producing higher peak concentrations (C(max)) than 5-mg extended-release epidural morphine sulfate, which produced more prolonged serum morphine concentrations. Using labeled doses of extended-release epidural morphine sulfate (10-20 mg), the C(max) was comparable to that for 5-mg standard epidural morphine sulfate, whereas the apparent terminal elimination half-life and area under the serum concentration-time curve were twofold to fourfold greater and consistent with dose-proportional exposure. The mean dose-normalized C(max) for extended-release epidural morphine sulfate was 25% higher for women versus men. Administering extended-release epidural morphine sulfate 15 minutes after the test dose mitigated any pharmacokinetic interaction. Extended-release epidural morphine sulfate demonstrated dose- related reductions in postoperative fentanyl consumption and pain intensity. CONCLUSION: A pooled analysis of six studies revealed that extended-release epidural morphine sulfate provided a more prolonged release of morphine compared with standard epidural morphine sulfate. Extended-release epidural morphine sulfate displayed a consistent pharmacokinetic profile among adults, with only slight variability between men and women in C(max), which appeared to be mainly caused by differences in body weight.