Clinical pharmacokinetics of chlordiazepoxide in patients with alcoholic hepatitis

The clearance of chlordiazepoxide from the systemic circulation was studied in 20 subjects which included 15 patients with alcoholic hepatitis and 5 normal volunteers. The half-life for the appearance of the drug in the systemic circulation was found to increase exponentially with age (r = 0.73, P less than 0.0005) and was independent of the presence of alcoholic hepatitis. The metabolic clearance of chlordiazepoxide was significantly lower in the patients than in the normal subjects (7.6 compared to 13.8 ml/kg-h, P less than 0.005). Linear regression analysis revealed a significant correlation between clearance and albumin (r = 0.77, P less than 0.00005). However, the predictive value of this relationship was shown to be minimal. Multiple regression analysis produced only a slight improvement in the correlation when both albumin and lactate dehydrogenase were used as variables (r = 0.83, P less than 0.00005). In six of the patients, a second clearance study was conducted three weeks following their initial one. All repeat subjects showed improvement both clinically and as reflected by their laboratory tests for liver injury, but there was not a significant change in their clearance of chlordiazepoxide. Multiple regression analysis of the clearance data on the initial and repeat subjects showed a significant correlation between clearance and the variables age, albumin and lactate dehydrogenase (r = 0.91, P less than 0.0025). This relationship suggests that over a short period of time (where age can be considered constant) changes in albumin and lactate dehydrogenase could be potentially useful in predicting clearance changes in a single individual.