Electrophysiologic and pharmacokinetic profile of the new antiarrhythmic drug TYB-3823 in humans.

Abstract

In an open-label study, electrophysiology and pharmacokinetics of TYB-3823, a new antiarrhythmic compound, were investigated. Sixteen patients underwent an electrophysiologic study before and after intravenous (i.v.) administration of TYB-3823. Two patients each received the following increasing doses: 0.2, 0.4, 0.8, and 1 mg/kg. Eight patients received 1.2-mg/kg. TYB-3823 concentrations followed a biexponential decrease with a terminal half-life (t1/2) of 3.88 +/- 0.87 h. Clearance was 47.2 +/- 18.5 L/h, and volume of distribution was 250 +/- 77 L. Dose-dependent pharmacokinetics were evident. Significant effects of TYB-3823 were apparent at doses > or = 0.8 mg/kg (n = 12), including increase in the AH and HV interval from 92 +/- 17 to 105 +/- 19 ms (p < 0.002) and 47 +/- 7 to 60 +/- 12 ms (p < 0.005), respectively. QRS duration was prolonged from 100 +/- 16 to 126 +/- 22 ms (p < 0.001), accompanied by an increase of the corrected QT interval from 425 +/- 28 to 465 +/- 37 ms (p < 0.002). The corrected JT interval remained unchanged, however, refractoriness did not change, but monophasic action potential duration (APD) tended to decrease. TYB-3823 appeared effective against reinduction of all arrhythmias observed during the control study [atrial fibrillation, atrioventricular (AV) nodal tachycardias]. TYB-3823 depresses conduction velocity significantly without prolonging refractoriness. Therefore, TYB-3823 may be classified as a class 1C antiarrhythmic. On the basis of the present results, additional class 1B activity cannot be excluded. TYB-3823 has antiarrhythmic properties, appears to be devoid of proarrhythmic effects, and is well tolerated.

• Authors: H J Crijns, B Oosterhuis, A C Wiesfeld, H De Bruin, C K Mensink, J H Jonkman, C Kozma, K I Lie
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 21 Issue 1 Pg. 1-6 (Jan 1993) ISSN: 0160-2446 [Print] United States
• PMID: 7678662 (Publication Type: Journal Article)

Chemical References

• Anti-Arrhythmia Agents
• Guanidines
• restacorin

Topics

• Action Potentials (drug effects)
• Adult
• Aged
• Anti-Arrhythmia Agents (administration & dosage, pharmacokinetics, pharmacology)
• Arrhythmias, Cardiac (drug therapy, physiopathology)
• Electrocardiography
• Female
• Guanidines (administration & dosage, blood, pharmacokinetics, pharmacology)
• Half-Life
• Heart Conduction System (drug effects, physiopathology)
• Humans
• Injections, Intravenous
• Male
• Middle Aged
• Tissue Distribution