Clinical consequences of the lipophilicity and plasma protein binding of antiarrhythmic drugs and active metabolites in man.

Abstract:

:In two series of antiarrhythmic drugs tested, as the octanol/water partition coefficient increases so do the following: elimination from the body by biotransformation, first-pass biotransformation in the liver and gastrointestinal tract after oral administration, protein binding to some extent, and penetration into brain tissue. Patients receiving lipophilic beta-adrenoreceptor blocking drugs may experience more central nervous system side effects than those receiving hydrophilic beta blockers. Structural modification of a drug, guided by the concept of bioisosterism, may allow the disassociation of therapeutic from toxic activities. Alpha-1 acid glycoprotein is the major plasma protein that binds the basic antiarrhythmic drugs. Antiarrhythmic drug metabolites are generally more polar (less lipophilic) and less plasma protein-bound than the parent drugs.

journal_name

Ann N Y Acad Sci

authors

Drayer DE

doi

10.1111/j.1749-6632.1984.tb14507.x

subject

Has Abstract

pub_date

1984-01-01 00:00:00

pages

45-56

eissn

0077-8923

issn

1749-6632

journal_volume

432

pub_type

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