Disease relevance of BIDISOMIDE

• Rapid infusions of bidisomide or disopyramide in conscious dogs: effect of myocardial infarction on acute tolerability [1].
• 1. The metabolism of bidisomide was investigated to examine how dose and mode of drug administration (i.e. diet admixture versus oral solution) affect the absorption and metabolism of bidisomide in the toxicity studies [2].
• Bidisomide (15 mg/kg/min) was well tolerated and antiarrhythmic in dogs with infarctions [1].
• In rats with ventricular arrhythmias induced by coronary artery reperfusion following a 5-min coronary occlusion, the antiarrhythmic effects of 5 mg/kg of bidisomide were similar to those of the same doses of MXT and DSP [3].
• Bidisomide (5 mg/kg) reduced the number of premature ventricular complexes and the incidence of ventricular tachycardia and ventricular fibrillation similarly to MXT and DSP in rats with ventricular arrhythmias induced by coronary artery occlusion [3].

High impact information on BIDISOMIDE

• Bidisomide (SC-40230), a new antiarrhythmic agent: initial study of tolerability and pharmacokinetics [4].
• Bioavailability was studied in 12 male volunteers, with each receiving 2.0 mg/kg of bidisomide, both orally and intravenously, in an open-label crossover trial [4].
• The cardiac and general haemodynamic effects of SC-40230, a newly developed anti-arrhythmic agent with both class 1a and 1b properties, were assessed in two different types of experiments using anaesthetised dogs, and in experiments using isolated cat papillary muscles [5].
• At the canine anti-arrhythmic dose (9 mg.kg-1 intravenously), SC-40230 decreased the maximum rate of rise of the left ventricular pressure (LV dP/dtmax) by 20% [5].
• In the converse series of experiments after treatment with isoproterenol, which caused a 20 to 30% reduction in APD and ERP, only bidisomide completely reversed the effect of 1 microM isoproterenol [6].

Biological context of BIDISOMIDE

• RESULTS: Bidisomide plasma AUC was significantly reduced following oral drug co-administration with breakfast compared to fasted-state controls in human subjects and in dogs independent of the composition of the solid cooked breakfast [7].
• Reduced systemic availability of an antiarrhythmic drug, bidisomide, with meal co-administration: relationship with region-dependent intestinal absorption [7].
• 2. The mass spectra of bidisomide metabolites indicate that the two major metabolic pathways of bidisomide were hydroxylation of the piperidine ring and N-dealkylation [8].
• Our results indicate that bidisomide binds to rat cardiac sodium channels and that the dissociation kinetics of bidisomide from the inactivated sodium channel is slower than that of disopyramide [9].

Anatomical context of BIDISOMIDE

• The enantiomeric ratio of bidisomide recovered in the feces was approximately 1 [10].
• This was attributed to the more rapid absorption of bidisomide in the duodenum and ileum (and/or possibly colon) [10].
• Bidisomide AUC was decreased since it was well absorbed in the upper but not lower small intestine [7].
• The oral absorption profile of unlabeled bidisomide was also studied after administration of a solution by a nasoenteric tube to different sites of the gastrointestinal tract (stomach, duodenum, jejunum, and ileum) [10].
• The effects of bidisomide, an antiarrhythmic agent, on sodium current (I(Na)) in isolated rat ventricular myocytes were investigated using a whole cell voltage clamp method [9].

Associations of BIDISOMIDE with other chemical compounds

• Oral non-caloric hydroxypropyl methylcellulose meals decreased bidisomide to the same extent as homogenized solid meals but did not lower disopyramide AUC [7].
• Human studies with bidisomide confirmed that the terminal phase elimination of this drug was much faster than that of disobutamide, with a half-life of about 11h [11].
• Electrophysiologic effects of an antiarrhythmic agent, bidisomide, on sodium current in isolated rat ventricular myocytes: comparison with mexiletine and disopyramide [9].
• Effect of folate supplementation on clinical chemistry and hematologic changes related to bidisomide administration in the rat [12].

Gene context of BIDISOMIDE

• Thymidine kinase and thymidylate synthase activity of the bone marrow cells were not altered by the bidisomide treatment [12].

Analytical, diagnostic and therapeutic context of BIDISOMIDE

• After a 10-minute zero-order intravenous infusion, bidisomide plasma levels could best be described in terms of a three-compartment pharmacokinetic model with the mean half-life values of alpha, beta, and gamma phases of 0.12, 1.77, and 12.3 hours, respectively [4].
• In this study the effects of three different antiarrhythmic agents, bidisomide, flecainide and dofetillide, each of which prolongs atrial ERP, were compared before and after treatment with isoproterenol, a beta-adrenergic agonist [6].
• METHODS: Bidisomide plasma levels, following oral administration and intravenous infusion in the fasted state and with various meal treatments, were determined in human subjects [7].
• Both drugs prolonged the ECG lead II P duration, PR interval (bidisomide more so than disopyramide), and QRS duration [1].

References