Pharmacokinetics of Anesthetics: Basic Theory for Clinical Application

Abstract

  Pharmacokinetics of anesthetics is predominantly dependent on hepatic blood flow or hepatic enzyme activity. Pharmacokinetics of drugs with a high hepatic extraction ratio is also predominantly dependent on hepatic blood flow, and conditions such as heart failure, intermittent positive pressure ventilation, and laparotomy decrease hepatic blood flow, resulting in decreased clearance. Pharmacokinetics of drugs with a low hepatic extraction ratio is predominantly dependent on hepatic enzyme activity. Cytochrome P450 is the predominant hepatic enzyme involved in the metabolism of anesthetics. Because of interindividual variation of the activity of P450 isozyme, there is a wide interindividual variation in the pharmacokinetics of drugs with a low hepatic extraction ratio. Competitive or non-competitive inhibition of the activity of these P450 isozymes by simultaneously administered drugs is important for elucidating the pharmacokinetics of agents with a low hepatic extraction ratio.