PMID: 3748010Sep 1, 1986Paper

Oxidation of quinidine by human liver cytochrome P-450

Molecular Pharmacology
F P GuengerichI A Blair

Abstract

The anti-arrhythmic quinidine has been reported to be a competitive inhibitor of the catalytic activities of human liver P-450DB, including sparteine delta 2-oxidation and bufuralol 1'-hydroxylation, and we confirmed the observation that submicromolar concentrations are strongly inhibitory. Human liver microsomes oxidize quinidine to the 3-hydroxy (Km 4 microM) and N-oxide (Km 33 microM) products, consonant with in vivo observations. Both bufuralol and sparteine inhibited microsomal quinidine 3-hydroxylation. Liver microsomes prepared from DA strain rats showed a relative deficiency in quinidine 3-hydroxylase activity in females compared to males. These observations might suggest that quinidine oxidation is catalyzed by the same P-450 forms that oxidize debrisoquine, bufuralol, and sparteine; i.e., rat P-450UT-H and P-450DB. However, neither of these two purified enzymes catalyzed quinidine 3-hydroxylation, and anti-P-450UT-H, which strongly inhibits human liver microsomal bufuralol 1'-hydroxylation, did not substantially inhibit quinidine 3-hydroxylation or N-oxygenation. P-450MP, the human S-mephenytoin 4-hydroxylase, also does not appear to oxidize quinidine but P-450NF, the human nifedipine oxidase, does. Anti-P-450NF inhib...Continue Reading

Related Concepts

Related Feeds

Antiarrhythmic Agents: Mechanisms of Action

Understanding the mechanism of action of antiarrhythmic agents is essential in developing new medications as treatment of cardiac arrhythmias is currently limited by the reduced availability of safe and effective drugs. Discover the latest research on Antiarrhythmic Agents: Mechanism of Action here.

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Anti-Arrhythmic Drug Therapies

Anti-arrhythmic drugs are used to prevent abnormal heart rhythms. These medications are used in conditions including, ventricular tachycardia, ventricular fibrillation and atrial fibrillation. Discover the latest research on anti-arrhythmic drug therapies here.