Morphine-6-glucuronide bioavailability

Pharmacokinetic properties Codeine (Sindrup and Brosen, 1995) has a good oral bioavailability. The compound is extensively metabolized by O- and N-demethylation followed by glucuronidation. The main metabolites are norcodeine, morphine and hydrocodeine and their glucuronides. There are indications (Yue et al., 1997), that the analgesic effect is reduced in persons with low CYP2D6 activity (poor metabolizers). 

Pharmacokinetic properties Ethylmorphine (Aasmundstad et al., 1995) has a reasonable oral bioavailability. Like codeine, it is metabolized by O- and N-desalkylation, leading to nor-ethylmorphine, morphine, nor-morphine, and the respective glucuronides. 

Although glucuronidation is thought to be less affected than oxidation in patients with cirrhosis [50], morphine clearance may be reduced and the half-life prolonged [27]. A reduction in first-pass metabolism could increase the bioavailability of oral morphine, but will also reduce the formation of the active (morphine-6-glucuronide) and inactive metabolites. The clinical significance of this is uncertain [50]. 

Morphine undergoes first-pass metabolism in the liver (low oral bioavailability). One of its metabolites, morphine-6-glucuronide, is highly active, contributing greatly to analgesia and causing possible toxicity in renal dysfunction. 

Penson RT, Joel SP, Roberts M, Gloyne A, Beckwith S, Slevin ML. The bioavailability and pharmacokinetics of subcutaneous, nebulized and oral morphine-6-glucuronide. Br J Clin Pharmacol 2002 53(4) 347-354. 

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