Altered Morphine Glucuronide and Bile Acid Disposition in Patients with Non-Alcoholic Steatohepatitis

The functional impact of altered drug transport protein expression on the systemic pharmacokinetics of morphine, hepatically-derived morphine glucuronide (morphine-3- and morphine-6-glucuronide), and fasting bile acids was evaluated in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH) compared to healthy subjects. The maximum concentration (C max ) and area under the concentration-time curve (AUC 0-last ) of morphine glucuronide in serum were increased in NASH patients (343 vs. 225nM and 58.8 vs. 37.2μM*min, respectively; P ≤0.005); morphine pharmacokinetics did not differ between groups. Linear regression analyses detected an association of NASH severity with increased morphine glucuronide C max and AUC 0-last ( P