title: Plasma morphine and morphine-6-glucuronide during chronic morphine therapy for cancer pain: plasma profiles, steady-state concentrations and the consequences of renal failure.
abstract: Morphine-6-glucuronide (M-6-G) is an active metabolite of morphine that may contribute to drug effects. To understand better the relationship between morphine and M-6-G in cancer patients receiving chronic therapy, we employed high performance liquid chromatography with electrochemical detection to measure: (1) morphine and M-6-G plasma concentrations following discontinuation of dosing in 2 patients, one receiving oral therapy and the other an intravenous infusion; (2) morphine and M-6-G concentrations in random blood samples taken at apparent steady state from 8 patients, 7 with normal renal function and 1 with mild renal insufficiency, who were receiving continuous morphine infusions; and (3) morphine and M-6-G concentrations in random blood samples taken over a period of weeks from 4 patients, 2 with stable and 2 with declining renal function. Results demonstrated a slightly slower decline in plasma M-6-G than morphine concentrations following drug discontinuation, as would be expected for metabolite and parent relationship; roughly similar M-6-G: morphine ratios (mean molar ratio = 1.22) across a broad range of morphine doses in patients with normal renal function; and an increase in this ratio over time in patients with progressive renal dysfunction. These data illustrate the kinetics of M-6-G in cancer patients receiving chronic morphine therapy and confirm the importance of renal function in determining the concentration of the metabolite.
authors.affiliation: Pain Service, Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021 U.S.A. Department of Neurology Cornell University Medical College, New York, NY 10021 U.S.A. Department of Pharmacology, Cornell University Medical College, New York, NY 10021 U.S.A.
authors.forename: Russell K
authors.initials: RK
authors.lastname: Portenoy
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Foley
authors.forename: James
authors.initials: J
authors.lastname: Stulman
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Khan
authors.forename: Jean
authors.initials: J
authors.lastname: Adelhardt
authors.forename: Mary
authors.initials: M
authors.lastname: Layman
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Cerbone
authors.forename: Charles E
authors.initials: CE
authors.lastname: Inturrisi
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009022:Morphine Derivatives / Q000097:blood* / Q000493:pharmacokinetics; D009369:Neoplasms / Q000150:complications*; D010146:Pain / Q000097:blood* / Q000188:drug therapy / Q000209:etiology
chemical_list: D009022:Morphine Derivatives; C035349:morphine-6-glucuronide; D009020:Morphine