Huet P M, Lelorier J
Clin Pharmacol Ther. 1980 Aug;28(2):208-15. doi: 10.1038/clpt.1980.152.
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.
在9名正常受试者（4名吸烟者和5名非吸烟者）以及6名无门静脉高压的慢性B型肝炎患者中，研究了具有高肝提取率的利多卡因（L）和吲哚菁绿（ICG）的动力学。在每位受试者静脉注射和口服给药后研究L的代谢。这些数据用于计算L的全身清除率和口服清除率、L的全身生物利用度以及表观肝血流量。在吸烟者中，由于口服清除率显著增加，L的全身生物利用度降低，这反映了药物代谢活性的诱导。在慢性肝炎患者中，L的全身清除率和口服清除率高于正常受试者。这些发现表明，在慢性B型肝炎患者中，肝脏对具有高肝提取率的药物（如L）的处理能力可能增强。通过将结果与肝静脉插管时使用ICG清除率和提取方法的结果进行比较，在5名患者中验证了L处置方法。口服给药后L的全身生物利用度反映了肝脏的首过清除率，可能是评估肝脏清除具有高肝提取率药物总体能力的一种有用的动力学方法。
