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Comparative Study
, 47 (1), 12-9

Morphine and Metabolite Behavior After Different Routes of Morphine Administration: Demonstration of the Importance of the Active Metabolite morphine-6-glucuronide

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Comparative Study

Morphine and Metabolite Behavior After Different Routes of Morphine Administration: Demonstration of the Importance of the Active Metabolite morphine-6-glucuronide

R Osborne et al. Clin Pharmacol Ther.

Abstract

The pharmacokinetic parameters of morphine, morphine-6-glucuronide, and morphine-3-glucuronide were studied after single-dose morphine administration by five different routes. The quantitative significance of the active metabolite morphine-6-glucuronide was assessed, and the effects of novel dosing forms on morphine metabolism and distribution were examined. After administration of intravenous morphine the morphine-6-glucuronide plasma AUC exceeded that of morphine. After administration of oral morphine very low morphine levels were observed--the morphine-6-glucuronide plasma AUC exceeded that of morphine by a factor of 9:1. Sublingual, buccal, and sustained-release buccal morphine tablet administration resulted in delayed absorption, with attenuation and delay of peak morphine and metabolite levels. Morphine bioavailability and morphine glucuronide production were not altered.

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