Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042510 (ventricular fibrillation)
 10,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The concentrations of quinidine, (3S)-3-hydroxyquinidine (3-OH), and 2'-oxoquinidinone (2'-OXO) in serum samples from 25 patients on long-term quinidine therapy were determined by a high-pressure liquid chromatography assay. Large individual variation in the levels of each of the compounds measured was observed. After correcting for differences in protein binding, the ratio of 3-OH/quinidine in serum water is 0.61 +/- 0.31 (SD) and the ratio of 2'-OXO/quinidine is 0.39 +/- 0.44. Seven of the 25 patients had serum water levels of one of these metabolites similar to or greater than that of quinidine. The quinidine levels, after normalizing for dose, are significantly higher in hemodialysis patients (about twice) than in nonazotemic patients; azotemic patients have mean values intermediate between them. Quinidine, 3-OH, and 2'-OXO are equally potent antiarrhythmic drugs (ED50 = 0.18, 0.17, and 0.21 mmoles/kg, respectively) when tested against chloroform- and hypoxia-induced ventricular fibrillation in mice. O-Desmethylquinidine, a new metabolite detected in urine of quinidine-treated patients, is less active. Quinidine and 2'-OXO are equally potent (ED50 = 0.010 mmoles/kg), while 3-OH seems less potent and more toxic when tested against BaCl2-induced ventricular arrhythmias in rabbits. Thus, these metabolites appear to contribute to the effects of quinidine and may make a significant contribution in some cases.
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PMID:Steady-state serum levels of quinidine and active metabolites in cardiac patients with varying degrees of renal function. 65 16

We investigated the antiarrhythmic activity of two major metabolites of quinidine in human, 3-hydroxyquinidine and quinidine-N-oxide, alone and in combination with the parent drug in an experimental model using reperfusion arrhythmias in an isolated rat heart preparation. No definite pharmacological activity could be shown for quinidine-N-oxide up to concentrations of 16 mg/l. Quinidine and 3-hydroxyquinidine prevented ventricular fibrillation and ventricular tachycardia after coronary reperfusion in a concentration-dependent manner. The relationship between the drug concentration in the perfusate and the fractional suppression of arrhythmia could be described adequately for both compounds by the Hill equation. Whereas no difference was found for the Hill coefficient, the estimates of the concentration associated with 50% arrhythmia suppression was significantly higher for 3-hydroxyquinidine (10.7 +/- 0.3 mg/l vs. 2.2 +/- 0.25 mg/l), indicating that the relative potency of the metabolite was only about 20% compared to the parent compound. To investigate the pharmacodynamic interaction of the two compounds the concentration-response curve was determined for quinidine also in the presence of 3-hydroxyquinidine at a constant concentration of 4 mg/l. A method has been derived that allows quantitative assessment of the pharmacodynamic interaction of two compounds for which the concentration-effect relationship can be described by the Hill equation. The results indicate that the antiarrhythmic effects of 3-hydroxyquinidine and quinidine are additive.
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PMID:Antiarrhythmic activity of two quinidine metabolites in experimental reperfusion arrhythmia: relative potency and pharmacodynamic interaction with the parent drug. 366 60