Less glucuronidation of morphine in the presence of ethanol in vivo

Abstract

Purpose: Ethanol and morphine are both substrates of uridine diphosphate glucuronosyl transferases (UGTs). A pharmacokinetic interaction between ethanol and morphine is suggested from in vitro studies, but to our knowledge not documented in vivo. The aim of this study was to compare the ratios between M6G and morphine and between M3G and morphine in blood samples from suspected drunk and drugged drivers, with and without presence of ethanol.

Methods: The data in the present study constitute all cases of suspected drunk and drugged driving positive for morphine, collected in Norway, in the period November 1st 2009 to December 1st 2012, during which all morphine positive cases were also routinely analysed for M6G and M3G. The cases were divided into two groups; one where morphine was present together with ethanol (group 1) and one where morphine was present in the absence of ethanol (group 2).

Results: The ratios between M3G and morphine was lower in the ethanol positive cases, i.e. mean 4.9 (95 % CI 4.03-5.79) in group 1 and mean 6.7 (95 % CI 6.35-7.00) in group 2 (p < 0.001). The ratios between M6G and morphine was also lower in the ethanol positive cases, i.e. mean 0.62 (95 % CI 0.42-0.81) in group 1 and mean 0.96 (95 % CI 0.89-1.02) in group 2 (p = 0.001).

Conclusions: This study indicated that the metabolism of morphine may be changed in the presence of ethanol, resulting in less formation of the metabolites. This could lead to increased terminal half-life for morphine and also possibly more accumulation after repeated dosing.