Context. Morphelan2 (morphine sulfate extended release), a new, once-daily, oral morphine sulfate formulation, releases morphine in a dual-release manner, providing an initial rapid delivery while maintaining therapeutic morphine concentrations throughout a 24-hour period with minimal fluctuation.
Objective. The primary objective of this study was to compare steady-state pharmacokinetic (PK) profiles of morphine and oxycodone following administration of 60 mg of Morphelan, once daily and 20 mg of OxyContin1 (oxycodone hydrochloride controlled release) twice daily, respectively.
Design, Setting, Participants, Intervention. Thirty-five healthy subjects were randomized to receive Morphelan once daily, or OxyContin twice daily for 7 days in this multiple-dose, open-label, parallel design study.
Measures. Blood samples were obtained on day 7 to determine differences, if any, in the PK parameters that characterize the ability of the formulations to control the release of drug. Safety data were collected throughout the study.
Results. Thirty-two subjects completed the study; 31 subjects were eligible for PK evaluation. The time to reach and maintain threshold concentrations of 50% or 75% of maximum was comparable for Morphelan and OxyContin. However, in comparison to OxyContin twice daily, once-daily Morphelan provided a statistically significantly reduced peak-to-trough fluctuation (%FI = 91% vs 77%, respectively, P= 0.05) and a lower number of fluctuations (2 vs 1, respectively) over a 24-hour period.
Conclusions. Once-daily Morphelan provided an initial rapid release of opioid reaching and maintaining threshold concentrations of 50% and 75% of maximum comparable to OxyContin twice daily. However, Morphelan provided more consistent opioid concentrations throughout a 24-hour period, with less frequent dosing.
Gourlay GK.Sustained relief of chronic pain. Pharmacokinetics of sustained release morphine. Clin Pharmacokinet. 1998;35:173-190.
2.
McCarberg BH, Barkin RL.Long-acting opioids for chronic pain: Pharmacotherapeutic opportunities to enhance compliance, quality of life, and analgesia. Am J Ther. 2001;8:181-186.
3.
Eliot L, Loewen G, Bulter J, Tembe E, Devane J.Steady-state pharmacokinetic comparison of Morphelan ROER (Morphine Sulfate Rapid Onset Extended Release) once-a-day and morphine oral solution administered q4h around-the-clock in healthy volunteers. American Academy of Pain Medicine (AAPM) 17th Annual Meeting. Miami, FL; 2001.
4.
Portenoy RK, Eliot L, Loewen G, Butler J, Tembe E, Devane J.Steady-state pharmacokinetic comparison of a new once-a-day dual-release oral morphine sulfate formulation and a twice-a-day controlled-release oral morphine formulation in patients with moderate-to-severe chronic pain. American Pain Society (APS) 20th Annual Meeting. Phoenix, AZ; 2001.
5.
Anonymous. International Marketing Survey (IMS) Healthy Data Survey. 2000.
6.
Mandema JW, Kaiko RF, Oshlack B, Reder RF, Stanski DR.Characterization and validation of a pharmacokinetic model for controlled-release oxycodone. Br J Clin Pharmacol. 1996;42:747-756.
7.
Reder RF, Oshlack B, Miotto JB, Benziger DD, Kaiko RF.Steady-state bioavailability of controlled-release oxycodone in normal subjects. Clin Ther. 1996;18:95-105.
8.
Metropolitan Life Insurance Company Height and Weight Table for Men. Copyright 1996. Metropolitan Life Insurance Company; 1999.
9.
and the 52nd WMA General Assembly, Edinburgh, Scotland, October 2000; 2000.
10.
Eliot L, Loewen G, Bulter J, Tembe E, Devane J.Sprinkle dosing of a new, once-a-day oral extended-release morphine formulation, Morphelan ROER. American Society of Clinical Oncology (ASCO) 37th Annual Meeting. San Francisco, CA; 2001.
11.
Mulleners WM, Whitmarsh TE, Steiner TJ.Noncompliance may render migraine prophylaxis useless, but once-daily regimens are better. Cephalal gia. 1998;18:52-56.
12.
Eisen SA, Miller DK, Woodward RS, Spitznagel E, Przybeck TR.The effect of prescribed daily dose frequency on patient medication compliance. Arch Intern Med. 1990;150:1881-1884.
13.
Farmer KC, Jacobs EW, Phillips CR.Long-term patient compliance with prescribed regimens of calcium channel blockers. Clin Ther. 1994;16:316-326; discussion 271-272.
