Clinical consequences of the lipophilicity and plasma protein binding of antiarrhythmic drugs and active metabolites in man.
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.
D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000889:Anti-Arrhythmia Agents / Q000009:adverse effects / Q000378:metabolism*; D001711:Biotransformation; D001798:Blood Proteins / Q000378:metabolism*; D002490:Central Nervous System / Q000187:drug effects; D006801:Humans; D050356:Lipid Metabolism; D011217:Practolol / Q000009:adverse effects; D011342:Procainamide / Q000009:adverse effects; D011485:Protein Binding; D012995:Solubility; D013329:Structure-Activity Relationship
D000319:Adrenergic beta-Antagonists; D000889:Anti-Arrhythmia Agents; D001798:Blood Proteins; D011342:Procainamide; D011217:Practolol