Pharmacokinetics and Pharmacodynamics of Landiolol Hydrochloride, an Ultra Short-acting β1-Selective Blocker, in a Dose Escalation Regimen in Healthy Male Volunteers
التفاصيل البيبلوغرافية
العنوان:
Pharmacokinetics and Pharmacodynamics of Landiolol Hydrochloride, an Ultra Short-acting β1-Selective Blocker, in a Dose Escalation Regimen in Healthy Male Volunteers
Summary: Objectives 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. Methods We set two-dose escalation regimen (LM and MH groups) using three different doses [L (low): 0.03 mg/kg/min (1 min) loadings → 0.01 mg/kg/min (10 min) continuous, M (medium): 0.06 mg/ kg /min (1 min) loadings → 0.02 mg/kg/min (10 min) continuous, H (high): 0.125 mg/kg/min (1 min) loadings → 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). Results 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. Conclusions The concentration of landiolol hydrochloride rapidly reached steady state levels, and rapidly dissipated after completion of administration.