title: Steady-state pharmacokinetic evaluation of a novel, controlled-release morphine suppository and subcutaneous morphine in cancer pain.
abstract: Although the oral route is the preferred method for morphine administration for cancer pain, many patients will require an alternate route of administration at some point during their illness. The authors studied the steady-state pharmacokinetics of morphine after administration of a novel, controlled-release suppository (MS-CRS) and subcutaneous morphine 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 absorption compared with subcutaneous morphine given every 4 hours (AUC0-12, 132.5 +/- 30.1 versus 123.8 +/- 27.3 ng.h.mL-1, P = not significant [NS]). Peak morphine concentrations were lower, time of peak was later, and percent fluctuation less after MS-CRS than after subcutaneous morphine (Cmax, 14.7 +/- 2.9 versus 29.9 +/- 5.4 ng/mL, P = .0110; tmax, 3.33 +/- 0.75 versus 2.22 +/- 0.15 hours, P = .0160; fluctuation, 122 +/- 71 versus 356 +/- 123%, P = .00160). Relative bioavailability of MS-CRS using the 2.5:1 analgesic ratio was 105%, and bioavailability from data dose normalized without regard to route specificity in metabolism was 42%. For both routes of administration there was a significant linear relationship between morphine dose and AUC (MS-CRS, r = .8568, P = .0032; subcutaneous morphine, r = .8314, P = .0055). MS-CRS morphine provides a pharmacokinetic profile consistent with dosing every 12 hours; at steady state, the extent of absorption is comparable with that of subcutaneous morphine when administered at a 2.5:1 dose ratio.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Palliative Care Medicine, University of Alberta and Edmonton General Hospital, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Bruera
authors.forename: R
authors.initials: R
authors.lastname: Fainsinger
authors.forename: K
authors.initials: K
authors.lastname: Spachynski
authors.forename: N
authors.initials: N
authors.lastname: Babul
authors.forename: Z
authors.initials: Z
authors.lastname: Harsanyi
authors.forename: A C
authors.initials: AC
authors.lastname: Darke
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009369:Neoplasms / Q000503:physiopathology; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D013488:Suppositories
chemical_list: D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D013488:Suppositories; D009020:Morphine