Pharmacokinetics of landiolol hydrochloride, a new ultra-short-acting beta-blocker, in patients with cardiac arrhythmias

Objectives: To elucidate pharmacokinetics and pharmacodynamics of landiolol hydrochloride, newer developed ultra-short-acting beta-blocker, in patient s with various cardiac tachyarrhythmias. Background: The short duration of action and titratability of landiolol hyd rochloride make it ideal for use in patients with a clinical need for beta- blockers. Methods: In a total of 31 examinations we infused the drug in 19 patients ( mean age, 55 +/- 14 years). After the persistence of the tachyarrhythmias w as confirmed, continuous infusion was started at rates of 0.005, 0.01, 0.02 , 0.04, and 0.08 mg/kg/min for 5 minutes (for paroxysmal atrial fibrillatio n, paroxysmal supraventricular tachycardia, and ventricular tachycardia) or 15 minutes (for ventricular premature complex). We analyzed the pharmacoki netics of 16 examinations. A one-compartment model provided a close fit for each blood concentration-time curve. Results: The maximum blood concentrations obtained clearly showed the dose dependency and revealed very short half-lives (range, 2.3 to 4.0 minutes). Area under the blood concentration-time curves also increased, showing dose dependency. In paroxysmal atrial fibrillation, landiolol hydrochloride red uced the heart rate from 111 +/- 20 to 90 +/- 10/min. Sinus rhythm was rest ored, without any adverse effects, in three of five patients with paroxysma l supraventricular tachycardia and one patient with ventricular tachycardia , There was no significant change in peripheral blood pressure, Conclusions: Landiolol hydrochloride has a shorter elimination half-life th an any other beta-blocker, and it can be administered safely to patients wi th various tachyarrhythmias.