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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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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Pharmacokinetics
Population
Healthy Volunteers
Heart Rate
Gynecologic Surgical Procedures
landiolol
Software
Anesthesia
Blood Pressure

Keywords

  • Landiolol hydrochloride
  • Pharmacokinetics
  • Target-controlled infusion

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Medicine(all)

Cite this

Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in gynecologic patients. / Kunisawa, Takayuki; Yamagishi, Akio; Suno, Manabu; Nakade, Susumu; Higashi, Ryunosuke; Kurosawa, Atsushi; Sugawara, Ami; Matsubara, Kazuo; Iwasaki, Hiroshi.

In: Journal of Anesthesia, Vol. 29, No. 2, 01.04.2015, p. 198-205.

Research output: Contribution to journalArticle

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, vol. 29, no. 2, pp. 198-205. https://doi.org/10.1007/s00540-014-1908-5
Kunisawa, Takayuki ; Yamagishi, Akio ; Suno, Manabu ; Nakade, Susumu ; Higashi, Ryunosuke ; Kurosawa, Atsushi ; Sugawara, Ami ; Matsubara, Kazuo ; Iwasaki, Hiroshi. / Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in gynecologic patients. In: Journal of Anesthesia. 2015 ; Vol. 29, No. 2. pp. 198-205.
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AU - Higashi, Ryunosuke

AU - Kurosawa, Atsushi

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N2 - 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.

AB - 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.

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