Metabolism and Excretion of Intravenous Drugs

Clearance of IV anesthetics from the body eventually requires metabolism and excretion. Since drugs with long elimination half-lives (t1/2f) will have slow rates of clearance, their use by repeated IV bolus or continuous infusion to maintain anesthesia has been restricted. Long-term application with limited concern for the pharmacokinetics of the agents may lead to delayed awakening, as large quantities of these drugs may accumulate in reservoir tissues, such as skeletal muscle and fat. Thus, after lengthy anesthetic administration, drug plasma levels will remain high as the compound diffuses from these tissue reservoirs. On the other hand, if the duration of an infusion remains short, awakening may be nearly the same with drugs exhibiting short and long elimination half-lives. With a shorter infusion, the quantities of drug accumulated in reservoir tissues are not sufficient to maintain high plasma and brain levels. Thus, length of infusion is a context in which the duration of drug action is considered. The term context sensitive half-time has been coined to express the effect of duration of infusion (the context) on plasma levels of infused drugs.

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