Pharmacokinetics and pharmacodynamics of landiolol hydrochloride, an ultra short-acting beta1-selective blocker, in a dose escalation regimen in healthy male volunteers

• Published in: Drug metabolism and pharmacokinetics Vol. 20; no. 5; pp. 337 - 344
• Main Authors: Murakami, Makoto, Furuie, Hidetoshi, Matsuguma, Kyoko, Wanibuchi, Atsuko, Kikawa, Shinichi, Irie, Shin
• Format: Journal Article
• Language: English
• Published: England 01-10-2005
• Subjects: Adrenergic beta-Antagonists - administration & dosage; Adrenergic beta-Antagonists - pharmacokinetics; Adrenergic beta-Antagonists - pharmacology; Adult; Blood Pressure - drug effects; Dose-Response Relationship, Drug; Double-Blind Method; Heart Rate - drug effects; Humans; Male; Morpholines - administration & dosage; Morpholines - pharmacokinetics; Morpholines - pharmacology; Urea - administration & dosage; Urea - analogs & derivatives; Urea - pharmacokinetics; Urea - pharmacology
• ISSN: 1347-4367

We conducted a randomized, double-blind, placebo-controlled study to evaluate the pharmacokinetics and pharmacodynamics of landiolol hydrochloride in a dose escalation regimen in healthy male volunteers.
We set two-dose escalation regimen (LM and MH groups) using three different doses [L (low): 0.03 mg/kg/min (1 min) loading-->0.01 mg/kg/min (10 min) continuous, M (medium): 0.06 mg/kg/min (1 min) loading-->0.02 mg/kg/min (10 min) continuous, H (high): 0.125 mg/kg/min (1 min) loading-->0.04 mg/kg/min (10 min) continuous]. Sixteen subjects were allocated randomly to the LM, MH, and placebo groups (n=6, 6, and 4, respectively).
In both the LM and MH groups, the blood concentration of landiolol hydrochloride changed within a constant range from 2 minutes after initiation of administration to just before the higher dose escalation. By 2 minutes following the higher dose escalation, the concentration of landiolol hydrochloride reached C(max), and reached almost steady state levels until 6 minutes following administration of the higher dose. The t(1/2) of landiolol hydrochloride was 3.5 minutes. The heart rates and blood pressures of subjects administered landiolol hydrochloride decreased, but there were no adverse events in any subject.
The concentration of landiolol hydrochloride rapidly reached steady state levels, and rapidly dissipated after completion of administration.