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Vol. 51, Issue 2, 135-158, June 1999
Drug Metabolism, Merck Research Laboratories, West Point,
Pennsylvania
I. Introduction
II. Physiological and Biochemical Factors Affecting Intestinal
Metabolism
A. Anatomy and Circulation of the Small Intestine
1. Mucosal Blood Flow
2. Countercurrent Exchange
B. Localization of Drug-Metabolizing Enzymes in the Small Intestine
1. Cytochromes P-450
2. UDP Glucosyltransferases and Sulfotransferases
C. Intestinal Enzyme Induction
1. Cytochromes P-450
2. UDP Glucosyltransferases
3. Effect of Route and Dose on Enzyme Induction
D. p-Glycoprotein
1. Intestinal p-Glycoprotein
2. Cytochromes P-450 and p-Glycoprotein
3. p-Glycoprotein and Intracellular Residence Time
III. Drug Absorption and Intestinal First-Pass Metabolism
A. Drug Absorption and Concentration Gradient
B. Saturable First-Pass Metabolism
C. Hepatic and Intestinal Organ Clearance
IV. Relative Contribution of Hepatic and Intestinal First-Pass
Metabolism
V. Conceptions and Misconceptions
VI. Conclusions
Acknowledgment
References
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