Effects of smoking and chronic hepatitis B on lidocaine and indocyanine green kinetics

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Abstract
Kinetics of lidocaine (L) and indocyanine green (ICG), substances with a high hepatic extraction ratio, was studied in 9 normal subjects (4 smokers and 5 nonsmokers) and in 6 patients with chronic type B hepatitis without portal hypertension. L metabolism was studied in each subject after i.v. and oral administration. The data were used to calculate L systemic and oral clearances, L systemic bioavailability and apparent hepatic blood flow. In smokers, L systemic bioavailability was decreased secondary to a marked increase in oral clearance, reflecting induction of drug-metabolizing activity. In patients with chronic hepatitis, L systemic and oral clearances were higher than in normal patients. Hepatic handling of drugs with a high hepatic extraction ratio, such as L, might be enhanced in patients with chronic type B hepatitis. The L disposition approach was validated in 5 patients by comparing results with those using the ICG clearance and extraction method at the time of hepatic vein catheterization. The L systemic bioavailability after oral administration is a reflection of 1st-pass clearance by the liver and might be a useful kinetic method for evaluating the overall ability of the liver to remove drugs with high hepatic extraction ratios.

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