Alanine Transaminase and Total Bilirubin Concentrations Predict CYP3A Activity

OBJECTIVE To investigate the activity of CYP3A in patients with different liver function and whether serum concentrations of liver function indices may predict the CYP3A activity. METHODS Forty-five patients undergoing operation under general anesthesia were enrolled in the study, including 15 cases with normal liver function (normal group), 15 cases with moderate fatty liver according to both the results of ultrasonic diagnosis of moderate fatty liver and the laboratory results of elevated alanine transaminase less than 3 times the normal (moderate injury group), and 15 cases with end-stage liver disease (end stage group). Each patient received single dose of 5 mg midazolam intravenously. CYP3A activity was measured by plasma 1’hydroxymidsazolam/midazolam (1’-OH-MDZ/MDZ) ratio at 2 h after administration of midazolam. The correlations between function indices and CYP3A activity were evaluated by multiple linear regression RESULTS There was no significant difference of CYP3A activity between the patients in normal group and moderate injury group (P=0.332). The activity of CYP3A in end stage group was lower than in normal group and moderate injury group (P=0.000). Multiple linear regression analysis showed a statistically significant linear relationship between the activity of CYP3A and alanine transaminase (ALT, R²=0.682, P=0.000), and total bilirubin (TB, R²=0.519, P=0.002). There were no other factors, including albumin (ALB, P=0.881) and alkaline phosphatase (ALP, P=0.497), correlated with the activity of CYP3A. CONCLUSION The activity of CYP3A in patients with end-stage liver disease decreased. Serum concentrations of ALT and TB have a predictive value for CYP3A in patient with liver dysfuntion.