Section 1 focuses on presystemic elimination by the gastrointestinal tract. This section discusses the enzymatic biotransformation in the gastrointestinal mucosa and the ability of the microflora to metabolize drugs. Section 2 considers the contribution of the liver to presystemic drug elimination, with a particular emphasis on the physiological factors, which determine the rate of breakdown of drugs in vivo. This section also deals with the effects of hepatic cirrhosis on presystemic drug elimination. Section 3 presents first a brief outline of the knowledge of pulmonary structure and relevant physiology, followed by a discussion on "first-pass¿ metabolism of endogenous substrates and drugs across the pulmonary circulation and of environmental chemicals after inhalation. This section also provides the methods for distinguishing between the contribution of the various sites to presystemic drug elimination and the problems associated with attempts to analyze available pharmacokinetic data.
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