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Vol. 50, Issue 1, 107-142, March 1998

Renal Drug Metabolism

James W. Lohra, Gail R. Willsky and Margaret A. Acara

Departments of Pharmacology and Toxicology, Biochemistry, and Medicine, School of Medicine and Biomedical Sciences, State University of New York, Buffalo and V.A. Medical Center, New York

I. Introduction
    A. History
    B. Methodology
        1. Clearance.
        2. Sperber technique in chickens.
        3. Isolated perfused kidney.
        4. Tissue Preparations.
        5. Molecular biology.
II. Renal Pathways for the Biotransformation of Drugs
    A. Cytochrome P450 Dependent Mixed Function Oxidase System
        1. Cytochrome P450 in the kidney.
        2. Drugs that induce cytochrome P450 proteins.
        3. Specific renal cytochrome P450 enzymes.
        4. Nondrug factors that affect cytochrome P450 enzymes in the kidney that may modulate kidney drug metabolism.
    B. N-Oxidation (Flavin-Containing Monooxygenases)
    C. Alcohol Oxidation
    D. Aldehyde Oxidation
    E. Oxidative Deamination (Monoamine Oxidase)
    F. Aldehyde and Ketone Reduction
        1. Aldehyde reductase.
        2. Ketone reductase.
        3. Other.
    G. Hydrolysis Mechanisms
        1. Ester and amide hydrolysis/carboxylesterase and amidase.
        2. Epoxide hydrolysis.
III. Phase II: Synthetic Conjugation Pathways
    A. Glucuronidation
        1. Isoforms.
        2. Substrates and kinetics.
        3. Induction of renal glucuronyl transferase.
        4. Localization.
        5. Relative contribution of renal glucuronidation.
    B. Sulfation
    C. Methylation
        1. N-methylation.
        2. O-methylation.
        3. S-methylation.
    D. Acetylation
    E. Glutathione Conjugation
    F. Mercapturic Acid Synthesis
    G. Amino Acid Conjugation
        1. Glycine conjugation.
        2. Glutamine conjugation.
    H. Cysteine Conjugate beta -Lyase
IV. Localization of Drug Metabolizing Enzymes in the Kidney
V. Effects of Renal Metabolism
Acknowledgments
References

a   Address correspondence to: Margaret Acara, Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, NY 14214. 

0031-6997/98/5001-0107$03.00/0
PHARMACOLOGICAL REVIEWS
Copyright © 1998 by The American Society for Pharmacology and Experimental Therapeutics


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