Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in gynecologic patients

Takayuki Kunisawa, Akio Yamagishi, Manabu Suno, Susumu Nakade, Ryunosuke Higashi, Atsushi Kurosawa, Ami Sugawara, Kazuo Matsubara, Hiroshi Iwasaki

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Abstract

Purpose: We previously determined the pharmacokinetic (PK) parameters of landiolol in healthy male volunteers. In this study, we evaluated the usefulness of target-controlled infusion (TCI) of landiolol hydrochloride and determined PK parameters of landiolol in gynecologic patients. Methods: Nine patients who were scheduled to undergo gynecologic surgery were enrolled. After inducing anesthesia, landiolol hydrochloride was administered at the target plasma concentrations of 500 and 1,000 ng/mL for each 30 min. A total of 126 data points of plasma concentration were collected from the patients and used for the population PK analysis. Furthermore, a population PK model was developed using the nonlinear mixed-effect modeling software. Results: The patients had markedly decreased heart rates (HRs) at 2 min after the initiation of landiolol hydrochloride administration; however, their blood pressures did not markedly change from the baseline value. The concentration time course of landiolol was best described by a 2-compartment model with lag time. The estimate of PK parameters were total body clearance (CL) 34.0 mL/min/kg, distribution volume of the central compartment (V1) 74.9 mL/kg, inter-compartmental clearance (Q) 70.9 mL/min/kg, distribution volume of the peripheral compartment (V2) 38.9 mL/kg, and lag time (ALAG) 0.634 min. The predictive performance of this model was better than that of the previous model. Conclusion: TCI of landiolol hydrochloride is useful for controlling HR, and the PK parameters of landiolol in gynecologic patients were similar to those in healthy male volunteers and best described by a 2-compartment model with lag time.

Original languageEnglish
Pages (from-to)198-205
Number of pages8
JournalJournal of Anesthesia
Volume29
Issue number2
DOIs
Publication statusPublished - Apr 1 2015

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Keywords

  • Landiolol hydrochloride
  • Pharmacokinetics
  • Target-controlled infusion

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Kunisawa, T., Yamagishi, A., Suno, M., Nakade, S., Higashi, R., Kurosawa, A., Sugawara, A., Matsubara, K., & Iwasaki, H. (2015). Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in gynecologic patients. Journal of Anesthesia, 29(2), 198-205. https://doi.org/10.1007/s00540-014-1908-5