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The Hepatic First‐Pass Metabolism of Problematic Drugs
Author(s) -
Lalka David,
Griffith Robert K.,
Cronenberger Carol L.
Publication year - 1993
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1993.tb04720.x
Subject(s) - propafenone , first pass effect , propranolol , drug metabolism , pharmacokinetics , verapamil , lidocaine , pharmacology , drug , metabolism , medicine , first pass , anesthesia , mathematics , arithmetic , calcium , atrial fibrillation
The first‐pass hepatic metabolism of a number of important therapeutic agents is inconsistent with traditional models that assume that the hepatic extraction ratio of a drug is constant in each individual (independent of the concentration of drug in the hepatic sinusoidal blood and also independent of the history of exposure to the drug). In this review, the authors examine the first‐pass metabolism of five “problematic drugs” (propranolol, lidocaine, propafenone, verapamil, and nitroglycerin). Each of these compounds has unique facets to its hepatic clearance and pharmacokinetics as well as striking similarities. Selected aspects of first‐pass metabolism are reviewed, and a theory that may explain some of the unusual behavior of the four lipophilic bases (propranolol, lidocaine, propafenone, and verapamil) is presented. Finally, the unusual and variable clearance of nitroglycerin is discussed.