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Steady-state pharmacokinetics of controlled release oral morphine sulphate in healthy subjects.

TitleSteady-state pharmacokinetics of controlled release oral morphine sulphate in healthy subjects.
Publication TypeJournal Article
Year of Publication1986
AuthorsSavarese JJ, Goldenheim PD, Thomas GB, Kaiko RF
JournalClin Pharmacokinet
Volume11
Issue6
Pagination505-10
Date Published1986 Nov-Dec
ISSN0312-5963
KeywordsAdult, Delayed-Action Preparations, Humans, Kinetics, Morphine
Abstract

The pharmacokinetics of oral morphine sulphate as controlled release tablets ('MS-Contin') and solution were compared at steady-state. Plasma morphine concentrations were determined over 24 hours following the last dose of each drug when given in a randomised, crossover fashion to healthy subjects. Radioimmunoassay was used, which was sensitive yet provided good specificity relative to high-performance liquid chromatography. Controlled release tablets had 86% the bioavailability of the solution. Although each dose of controlled release tablets was double that of the solution, their peak plasma concentrations were the same. Time to maximum concentration was 3 times longer for controlled release tablets with an absorption half-life twice that of the solution. Elimination of both drugs was similar and biphasic with the minor terminal portion at 10 times the half-life of the major early process. These data explain the analgesic duration of 12 hours observed in clinical studies and the lack of accumulation with morphine compared with methadone.

DOI10.2165/00003088-198611060-00006
Alternate JournalClin Pharmacokinet
PubMed ID3802690