Effects of smoking and chronic hepatitis B on lidocaine and indocyanine green kinetics.
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 intravenous 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 the normal. These findings indicate that hepatic handling of drugs with a high hepatic extraction ratio, such as L, might be enhanced in patients with chronic type B hepatitis. 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 first-pass clearance by the liver and might be a useful kinetic method for evaluating overall ability of the liver to remove drugs with high hepatic extraction ratios.
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002908:Chronic Disease; D005260:Female; D006509:Hepatitis B / Q000378:metabolism*; D006801:Humans; D007208:Indocyanine Green / Q000378:metabolism*; D007700:Kinetics; D008012:Lidocaine / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects; D008103:Liver Cirrhosis / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D012907:Smoking / Q000503:physiopathology*
D008012:Lidocaine; D007208:Indocyanine Green