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Clinical Implications of the Competitive Inhibition of the Debrisoquin-Metabolizing Isozyme by Quinidine

Clinical Implications of the Competitive Inhibition of the Debrisoquin-Metabolizing Isozyme by... Abstract Approximately 10% of western populations are genetically deficient in the enzyme that metabolizes the antihypertensive drug debrisoquin. These "poor metabolizers" process many common medications in an aberrant fashion, resulting in a variety of untoward consequences including exaggerated drug effect, subtherapeutic drug concentrations, or complex drug interactions. A variety of medications, including neuroleptics, antidepressants, β-blockers, and certain antiarrhythmics, are subject to the influence of this metabolic polymorphism. Quinidine administration changes persons to poor metabolizers of debrisoquin for the duration of therapy. Thus, the use of quinidine with any of the other drugs metabolized by this isozyme may be expected to result in a drug interaction in which a person's response will mimic that of a poor metabolizer. Because no test is commonly available to determine directly the debrisoquin metabolic phenotype, clinicians should be alert to unusual drug reactions in patients receiving quinidine concurrently with the other medications. (Arch Intern Med. 1991;151:1985-1992) References 1. Szorady I. Pharmacogenetics, Principles and Paediatric Aspects . Budapest, Hungary: Publishing House of the Hungarian Academy of Science; 1973. 2. Kalow W. Race and therapeutic drug response . N Engl J Med. 1989;320:588-590.Crossref 3. Vessell ES. Pharmacogenetic perspectives: genes, drugs and disease . Hepatology. 1984;4:959-965.Crossref 4. Zhou HH, Koshakji RP, Silberstein DJ, Wilkinson GR, Wood AJJ. Altered sensitivity to and clearance of propranolol in men of Chinese descent as compared with American whites: racial differences in drug response . N Engl J Med. 1989;320:565-570.Crossref 5. Breimer DD. Interindividual variations in drug disposition . Clin Pharmacokinet. 1983;8:371-377.Crossref 6. 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Clinical Implications of the Competitive Inhibition of the Debrisoquin-Metabolizing Isozyme by Quinidine

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American Medical Association
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Copyright © 1991 American Medical Association. All Rights Reserved.
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0003-9926
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1538-3679
DOI
10.1001/archinte.1991.00400100065011
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Abstract

Abstract Approximately 10% of western populations are genetically deficient in the enzyme that metabolizes the antihypertensive drug debrisoquin. These "poor metabolizers" process many common medications in an aberrant fashion, resulting in a variety of untoward consequences including exaggerated drug effect, subtherapeutic drug concentrations, or complex drug interactions. A variety of medications, including neuroleptics, antidepressants, β-blockers, and certain antiarrhythmics, are subject to the influence of this metabolic polymorphism. Quinidine administration changes persons to poor metabolizers of debrisoquin for the duration of therapy. Thus, the use of quinidine with any of the other drugs metabolized by this isozyme may be expected to result in a drug interaction in which a person's response will mimic that of a poor metabolizer. Because no test is commonly available to determine directly the debrisoquin metabolic phenotype, clinicians should be alert to unusual drug reactions in patients receiving quinidine concurrently with the other medications. (Arch Intern Med. 1991;151:1985-1992) References 1. Szorady I. Pharmacogenetics, Principles and Paediatric Aspects . Budapest, Hungary: Publishing House of the Hungarian Academy of Science; 1973. 2. Kalow W. Race and therapeutic drug response . N Engl J Med. 1989;320:588-590.Crossref 3. Vessell ES. Pharmacogenetic perspectives: genes, drugs and disease . Hepatology. 1984;4:959-965.Crossref 4. Zhou HH, Koshakji RP, Silberstein DJ, Wilkinson GR, Wood AJJ. Altered sensitivity to and clearance of propranolol in men of Chinese descent as compared with American whites: racial differences in drug response . N Engl J Med. 1989;320:565-570.Crossref 5. Breimer DD. Interindividual variations in drug disposition . Clin Pharmacokinet. 1983;8:371-377.Crossref 6. 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Journal

Archives of Internal MedicineAmerican Medical Association

Published: Oct 1, 1991

References