Electrophysiologic and Pharmacokinetic Profile of the New Antiarrhythmic Drug TYB-3823 in Humans

Crijns, HJ., Oosterhuis, B., Wiesfeld, ACP., De Bruin, H., Mensink, CK., Jonkman, JHG., Kozma, C. & Lie, KI., Jan-1993, In : Journal of Cardiovascular Pharmacology. 21, 1, p. 1-6 6 p.

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  • HJ Crijns
  • B Oosterhuis
  • ACP Wiesfeld
  • H De Bruin
  • CK Mensink
  • JHG Jonkman
  • C Kozma
  • KI Lie

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 greater-than-or-equal-to 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 IC antiarrhythmic. On the basis of the present results, additional class IB activity cannot be excluded. TYB-3823 has antiarrhythmic properties, appears to be devoid of proarrhythmic effects, and is well tolerated.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Issue number1
Publication statusPublished - Jan-1993



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