STEADY-STATE PHARMACOKINETIC EVALUATION OF A NOVEL, CONTROLLED-RELEASE MORPHINE SUPPOSITORY AND SUBCUTANEOUS MORPHINE IN CANCER PAIN

Although the oral route is the preferred method for morphine administr ation for cancer pain, many patients will require an alternate route o f administration at some point during their illness. The authors studi ed the steady-state pharmacokinetics of morphine after administration of a novel, controlled-release suppository (MS-CRS) and subcutaneous m orphine in a randomized, double-blind, two-way crossover evaluation in 10 patients with cancer pain. When administered at a 2.5:1 analgesic ratio, MS-CRS given every 12 hours showed an equivalent extent of abso rption compared with subcutaneous morphine given every 4 hours (AUC(0- 12), 132.5 +/- 30.1 versus 123.8 +/- 27.3 ng . h . ml(-1), P = not sig nificant [NS]). Peak morphine concentrations were lower, time of peak was later, and percent fluctuation less after MS-CRS than after subcut aneous morphine (C-max, 14. 7 +/- 2.9 versus 29.9 +/- 5.4 ng/mL, P =.0 110; t(max), 3.33 +/- 0.75 versus 2.22 +/- 0.15 hours, P = .0160; fluc tuation, 122 +/- 71 versus 356 +/- 123%, P = .00160). Relative bioavai lability of MS-CRS using the 2.5:1 analgesic ratio was 105%, and bioav ailability from data dose normalized without regard to route specifici ty in metabolism was 42%. For both routes of administration there was a significant linear relationship between morphine dose and AUC (MS-CR S, r = .8568, P = .0032; subcutaneous morphine, r = .8314, P = .0055). MS-CRS morphine provides a pharmacokinetic profile consistent with do sing every 12 hours; at steady state, the extent of absorption is comp arable with that of subcutaneous morphine when administered at a 2.5:1 dose ratio. MS-CRS represents a reliable, noninvasive alternative met hod of morphine administration for patients unable to take oral morphi ne.