Treatment of Chronic Liver Disease. Do Cytoprotective Agents Interfere with Drug-Metabolizing Activity?

Abstract

There is evidence that interferon (IFN) depresses antipyrine and theophylline clearances, thus impairing the drug-metabolizing activity (DMA), whereas ursodeoxycholic acid (UDCA) treatment is associated with controversial findings regarding changes in quantitative liver function tests (LFTs). IFN (Intron A, 6 million units (MU) tiw), a membrane-stabilizing agent — UDCA (Deursil, 600 mg/day) and a new formulation of a free-radical scavenger — silibinin s cyclodextrin (IBI/S, 135 mg/day) were given to a total of 32 patients with chronic liver disease for 6 months. Liver function, as assessed by routine LFTs and the formation of monoethylglycinexylidide (MEGX) from lidocaine (1 mg/kg iv), was evaluated before and after treatment. For comparison, LFTs and MEGX were also estimated in 10 matched patients with chronic liver disease who received no therapy for 6 months. In the IFN-treated patients the 45-min MEGX values (normal value = 79.1 ± 3.3 ng/ml) were 58.2 ±4.9 at time 0 and increased by 20% during treatment (69.8 ± 5.0); mean ALT levels decreased from 173 ± 20 U/L at time 0 to 98 ± 22 after treatment (p <0.02); AST decreased by 27% whereas γ-GT levels did not vary significantly. MEGX values were virtually unchanged during UDCA and IBI/S administration (respectively, 45.5±5.2 and 53.7±7.6 at entry vs. 47.7±6.3 and 57.4±5.7 at month 6) whereas transaminase levels decreased by 16–30% after UDCA treatment and by 9–19% after IBI/S treatment. Moreover, UDCA and IBI/S caused a 36% and a 24% reduction of γ-GT levels, respectively. In the control group, MEGX values remained stable throughout the 6-month period and so did transaminase and γ-GT levels. Moreover, no correlation was found between the changes in LFTs and the 45-min MEGX values in any of the groups studied. Thus, in patients with chronic liver disease, a 6 months’ treatment with different cytoprotective agents was associated with an improvement in the common markers of liver function but with no significant changes in MEGX formation. These results suggest a lack of interference of tested drugs with DMA and favour the association of various cytoprotective agents with improved treatment outcome.