Population pharmacokinetics of landiolol hydrochloride in healthy subjects

Naoki Honda, Susumu Nakade, Hidefumi Kasai, Yoshitaka Hashimoto, Tomoya Ohno, Junsaku Kitagawa, Akinori Yamauchi, Chihiro Hasegawa, Shinichi Kikawa, Takayuki Kunisawa, Yusuke Tanigawara, Yasuyuki Miyata

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Landiolol hydrochloride is a newly developed cardioselective, ultra short-acting β1-adrenergic receptor blocking agent used for perioperative arrhythmia control. The objective of this study was to characterize the population pharmacokinetics of landiolol hydrochloride in healthy male subjects. A total of 420 blood concentration data points collected from 47 healthy male subjects were used for the population pharmacokinetic analysis. NONMEM was used for population pharmacokinetic analysis. In addition, the final pharmacokinetic model was evaluated using a bootstrap method and a leave-one-out cross validation method. The concentration time course of landiolol hydrochloride was best described by a two-compartment model with lag time. The final parameters were total body clearance (CL: 36.6 mL/min/kg), distribution volume of the central compartment (V1: 101 mL/kg), inter-compartmental clearance (16.1 mL/min/kg), distribution volume of the peripheral compartment (55.6 mL/kg), and lag time (0.82 min). The inter-individual variability in the CL and V1 were 21.8% and 46.3%, respectively. The residual variability was 22.1%. Model evaluation by the two different methods indicated that the final model was robust and parameter estimates were reasonable. The population pharmacokinetic model for landiolol hydrochloride in healthy subjects was developed and was shown to be appropriate by both bootstrap and leave-one-out cross validation methods.

Original languageEnglish
Pages (from-to)447-455
Number of pages9
JournalDrug Metabolism and Pharmacokinetics
Volume23
Issue number6
DOIs
Publication statusPublished - 2008

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Healthy Volunteers
Pharmacokinetics
Population
Adrenergic Antagonists
Adrenergic Receptors
Cardiac Arrhythmias
landiolol

Keywords

  • Bootstrap
  • Cross validation
  • Landiolol hydrochloride
  • Population pharmacokinetics
  • Ultra short-actingβ-adrenergic receptor blocking agent

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Pharmaceutical Science

Cite this

Honda, N., Nakade, S., Kasai, H., Hashimoto, Y., Ohno, T., Kitagawa, J., ... Miyata, Y. (2008). Population pharmacokinetics of landiolol hydrochloride in healthy subjects. Drug Metabolism and Pharmacokinetics, 23(6), 447-455. https://doi.org/10.2133/dmpk.23.447

Population pharmacokinetics of landiolol hydrochloride in healthy subjects. / Honda, Naoki; Nakade, Susumu; Kasai, Hidefumi; Hashimoto, Yoshitaka; Ohno, Tomoya; Kitagawa, Junsaku; Yamauchi, Akinori; Hasegawa, Chihiro; Kikawa, Shinichi; Kunisawa, Takayuki; Tanigawara, Yusuke; Miyata, Yasuyuki.

In: Drug Metabolism and Pharmacokinetics, Vol. 23, No. 6, 2008, p. 447-455.

Research output: Contribution to journalArticle

Honda, N, Nakade, S, Kasai, H, Hashimoto, Y, Ohno, T, Kitagawa, J, Yamauchi, A, Hasegawa, C, Kikawa, S, Kunisawa, T, Tanigawara, Y & Miyata, Y 2008, 'Population pharmacokinetics of landiolol hydrochloride in healthy subjects', Drug Metabolism and Pharmacokinetics, vol. 23, no. 6, pp. 447-455. https://doi.org/10.2133/dmpk.23.447
Honda, Naoki ; Nakade, Susumu ; Kasai, Hidefumi ; Hashimoto, Yoshitaka ; Ohno, Tomoya ; Kitagawa, Junsaku ; Yamauchi, Akinori ; Hasegawa, Chihiro ; Kikawa, Shinichi ; Kunisawa, Takayuki ; Tanigawara, Yusuke ; Miyata, Yasuyuki. / Population pharmacokinetics of landiolol hydrochloride in healthy subjects. In: Drug Metabolism and Pharmacokinetics. 2008 ; Vol. 23, No. 6. pp. 447-455.
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