Effect of route of administration and distribution on drug action

The extent and time course of drug action can be markedly affected by the route of drug administration into the patient as well as the pattern of drug distribution within the patient. Drugs which are rapidly cleared by hepatic processes will show a decreased extent of availability following oral administration due to metabolism of drug on its first pass through the liver. The magnitude of this first pass will depend on the blood flow to the liver and the intrinsic clearing ability of the liver (i.e., the ability of the organ to eliminate the drug independent of the rate at which drug is brought to the organ). Drug distribution in the patient will depend on the blood flow to various sites in the body as well as the partition coefficient of the drug between the blood and the distributive organs. Protein binding both in the plasma and in the tissues will markedly affect this distribution. However, free drug concentrations are generally believed to be the effective determinant in drug therapy. Often a redistribution due to changes in protein binding will have little effect on the therapeutic efficacy since, although total drug distribution changes, free concentrations in the plasma remain essentially similar.This article is extracted from the forthcoming bookModern Pharmaceutics: Drug Product Design and Evaluation, edited by Gilbert S. Banker and Christopher T. Rhodes, copyright 1978, Marcel Dekker, Inc. Published with permission.