LeLorier J, Moisan R, Gagné J, Caillé G
J Pharmacol Exp Ther. 1977 Dec;203(3):507-11.
Lidocaine is a commonly used and efficacious antiarrhythmic agent whose pharmacokinetics after a rapid intravenous bolus injection have been extensively studied. Due to its short half-life, a continuous infusion of lidocaine is necessary whenever therapeutic blood levels need to be maintained for prolonged periods of time. Recent work in man has shown that the elimination of lidocaine is much slower after a prolonged infusion than after a bolus. We present the results of a pharmacokinetic study of the disposition of lidocaine after the discontinuation of short (90 minutes) and long (24 hours) intravenous infusions which demonstrate that in both cases the elimination of lidocaine is best explained by a two-compartment open model with elimination from the central compartment and that the longer half-life of lidocaine after a prolonged infusion is due to an impairment of its hepatic extraction. Lidocaine hepatic elimination data obtained at the end of short- and long-term infusions confirmed the inferences drawn from the pharmacokinetic analysis by demonstrating that a long-term infusion produces an important decrease in the arterial clearance and hepatic extraction rate of lidocaine.
利多卡因是一种常用且有效的抗心律失常药物，其快速静脉推注后的药代动力学已得到广泛研究。由于其半衰期短，每当需要长时间维持治疗血药浓度时，就需要持续输注利多卡因。最近在人体上的研究表明，长时间输注后利多卡因的消除比推注后要慢得多。我们呈现了一项药代动力学研究的结果，该研究观察了短时间（90分钟）和长时间（24小时）静脉输注停止后利多卡因的处置情况，结果表明，在这两种情况下，利多卡因的消除最好用具有从中央室消除的二室开放模型来解释，并且长时间输注后利多卡因较长的半衰期是由于其肝脏摄取受损所致。在短期和长期输注结束时获得的利多卡因肝脏消除数据证实了从药代动力学分析得出的推论，即长期输注会使利多卡因的动脉清除率和肝脏摄取率显著降低。
