MULTIPLE-DOSE PHARMACOKINETIC EVALUATION OF 2 FORMULATIONS OF SUSTAINED-RELEASE MORPHINE-SULFATE TABLETS

Two sustained-release morphine products are available in the United St ates for the treatment of chronic pain requiring opioid analgesic medi cation for more than a few days. Oramorph SR(R) is indicated for every 12-hour administration and MS Contin(R) is indicated for every 8-to 1 2-hour administration. This study was conducted to evaluate the compar ative bioavailability of these two sustained-release forms of morphine using a multiple-dose, two-way crossover design in 26 healthy, adult male volunteers. Twenty-four male volunteers, aged 22 to 47 years (mea n, 31 years), weighing 139.0 to 220.0 pounds (mean, 171.4 pounds) and with height ranging from 66.5 to 75.5 inches (mean 69.8 inches) succes sfully completed the study. The means and standard deviations of the p harmacokinetic parameters are listed for Oramorph SR and MS Contin, re spectively: mean peak concentrations were 22.61 +/- 5.83 ng/mL and 24. 28 +/- 5.28 ng/mL, time to peak concentrations (T-max) were 3.75 +/- 1 .21 hours and 3.48 +/- 1.25 hours, area under the curves between 72 an d 84 hours since the first dose were 207.37 +/- 53.41 ng . hr/mL and 2 05.14 +/- 43.52 ng . hr/mL, average serum concentrations were 17.28 +/ - 4.45 ng/mL and 17.10 +/- 3.63 ng/mL, and the mean trough concentrati ons (C-min) were 11.06 +/- 3.64 ng/mL and 9.23 +/- 2.94 ng/mL. All of the above parameters met the 90% confidence intervals for the two, one -sided t test analysis except for C-min, which was higher for Oramorph SR and the T(m)ax, which showed high variability with both products. While 76.9% of the volunteers experienced at least one adverse event, there was no difference in the incidence of adverse events between the two products. The results of this study indicate that Oramorph SR and MS Contin provide equivalent amounts of morphine to the bloodstream o ver time in a multiple-dose, steady-state study design, with an equiva lent rate of absorption.