Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in patients with peripheral arterial disease

Takayuki Kunisawa, Akio Yamagishi, Manabu Suno, Susumu Nakade, Naoki Honda, Atsushi Kurosawa, Ami Sugawara, Yoshikazu Tasaki, Hiroshi Iwasaki

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Purpose: We previously determined the pharmacokinetic (PK) parameters of landiolol in healthy male volunteers and gynecological patients. In this study, we determined the PK parameters of landiolol in patients with peripheral arterial disease.

Methods: Eight patients scheduled to undergo peripheral arterial surgery were enrolled in the study. After inducing anesthesia, landiolol hydrochloride was administered at target plasma concentrations of 500 and 1,000 ng/mL for 30 minutes each. A total of 112 data points of plasma concentration were collected from the patients and used for the population PK analysis. A population PK model was developed using a nonlinear mixed-effect modeling software program (NONMEM).

Results: The patients had markedly decreased heart rates at 2 minutes after initiation of landiolol hydrochloride administration; however, systolic blood pressures were lower than the baseline values at only five time points. The concentration time course of landiolol was best described by a two-compartment model with lag time. The estimates of PK parameters were as follows: total body clearance, 30.7 mL/min/kg; distribution volume of the central compartment, 65.0 mL/kg; intercompartmental clearance, 48.3 mL/min/kg; distribution volume of the peripheral compartment, 54.4 mL/kg; and lag time, 0.633 minutes. The predictive performance of this model was better than that of the previous model.

Conclusion: The PK parameters of landiolol were best described by a two-compartment model with lag time. Distribution volume of the central compartment and total body clearance of landiolol in patients with peripheral arterial disease were approximately 64% and 84% of those in healthy volunteers, respectively.

Original languageEnglish
Pages (from-to)107-114
Number of pages8
JournalTherapeutics and Clinical Risk Management
Volume11
DOIs
Publication statusPublished - Jan 17 2015

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Pharmacokinetics
Peripheral Arterial Disease
Disease
Population
Healthy Volunteers
Plasmas
Blood Pressure
Blood pressure
surgery
Surgery
landiolol
time
Software
Anesthesia
Heart Rate
performance
Values

Keywords

  • Landiolol hydrochloride
  • PAD
  • Peripheral arterial disease
  • Pharmacokinetic parameters
  • Pharmacokinetics
  • Target-controlled infusion
  • TCI

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Medicine(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Safety Research
  • Chemical Health and Safety

Cite this

Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in patients with peripheral arterial disease. / Kunisawa, Takayuki; Yamagishi, Akio; Suno, Manabu; Nakade, Susumu; Honda, Naoki; Kurosawa, Atsushi; Sugawara, Ami; Tasaki, Yoshikazu; Iwasaki, Hiroshi.

In: Therapeutics and Clinical Risk Management, Vol. 11, 17.01.2015, p. 107-114.

Research output: Contribution to journalArticle

Kunisawa, Takayuki ; Yamagishi, Akio ; Suno, Manabu ; Nakade, Susumu ; Honda, Naoki ; Kurosawa, Atsushi ; Sugawara, Ami ; Tasaki, Yoshikazu ; Iwasaki, Hiroshi. / Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in patients with peripheral arterial disease. In: Therapeutics and Clinical Risk Management. 2015 ; Vol. 11. pp. 107-114.
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abstract = "Purpose: We previously determined the pharmacokinetic (PK) parameters of landiolol in healthy male volunteers and gynecological patients. In this study, we determined the PK parameters of landiolol in patients with peripheral arterial disease.Methods: Eight patients scheduled to undergo peripheral arterial surgery were enrolled in the study. After inducing anesthesia, landiolol hydrochloride was administered at target plasma concentrations of 500 and 1,000 ng/mL for 30 minutes each. A total of 112 data points of plasma concentration were collected from the patients and used for the population PK analysis. A population PK model was developed using a nonlinear mixed-effect modeling software program (NONMEM).Results: The patients had markedly decreased heart rates at 2 minutes after initiation of landiolol hydrochloride administration; however, systolic blood pressures were lower than the baseline values at only five time points. The concentration time course of landiolol was best described by a two-compartment model with lag time. The estimates of PK parameters were as follows: total body clearance, 30.7 mL/min/kg; distribution volume of the central compartment, 65.0 mL/kg; intercompartmental clearance, 48.3 mL/min/kg; distribution volume of the peripheral compartment, 54.4 mL/kg; and lag time, 0.633 minutes. The predictive performance of this model was better than that of the previous model.Conclusion: The PK parameters of landiolol were best described by a two-compartment model with lag time. Distribution volume of the central compartment and total body clearance of landiolol in patients with peripheral arterial disease were approximately 64{\%} and 84{\%} of those in healthy volunteers, respectively.",
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AU - Kunisawa, Takayuki

AU - Yamagishi, Akio

AU - Suno, Manabu

AU - Nakade, Susumu

AU - Honda, Naoki

AU - Kurosawa, Atsushi

AU - Sugawara, Ami

AU - Tasaki, Yoshikazu

AU - Iwasaki, Hiroshi

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N2 - Purpose: We previously determined the pharmacokinetic (PK) parameters of landiolol in healthy male volunteers and gynecological patients. In this study, we determined the PK parameters of landiolol in patients with peripheral arterial disease.Methods: Eight patients scheduled to undergo peripheral arterial surgery were enrolled in the study. After inducing anesthesia, landiolol hydrochloride was administered at target plasma concentrations of 500 and 1,000 ng/mL for 30 minutes each. A total of 112 data points of plasma concentration were collected from the patients and used for the population PK analysis. A population PK model was developed using a nonlinear mixed-effect modeling software program (NONMEM).Results: The patients had markedly decreased heart rates at 2 minutes after initiation of landiolol hydrochloride administration; however, systolic blood pressures were lower than the baseline values at only five time points. The concentration time course of landiolol was best described by a two-compartment model with lag time. The estimates of PK parameters were as follows: total body clearance, 30.7 mL/min/kg; distribution volume of the central compartment, 65.0 mL/kg; intercompartmental clearance, 48.3 mL/min/kg; distribution volume of the peripheral compartment, 54.4 mL/kg; and lag time, 0.633 minutes. The predictive performance of this model was better than that of the previous model.Conclusion: The PK parameters of landiolol were best described by a two-compartment model with lag time. Distribution volume of the central compartment and total body clearance of landiolol in patients with peripheral arterial disease were approximately 64% and 84% of those in healthy volunteers, respectively.

AB - Purpose: We previously determined the pharmacokinetic (PK) parameters of landiolol in healthy male volunteers and gynecological patients. In this study, we determined the PK parameters of landiolol in patients with peripheral arterial disease.Methods: Eight patients scheduled to undergo peripheral arterial surgery were enrolled in the study. After inducing anesthesia, landiolol hydrochloride was administered at target plasma concentrations of 500 and 1,000 ng/mL for 30 minutes each. A total of 112 data points of plasma concentration were collected from the patients and used for the population PK analysis. A population PK model was developed using a nonlinear mixed-effect modeling software program (NONMEM).Results: The patients had markedly decreased heart rates at 2 minutes after initiation of landiolol hydrochloride administration; however, systolic blood pressures were lower than the baseline values at only five time points. The concentration time course of landiolol was best described by a two-compartment model with lag time. The estimates of PK parameters were as follows: total body clearance, 30.7 mL/min/kg; distribution volume of the central compartment, 65.0 mL/kg; intercompartmental clearance, 48.3 mL/min/kg; distribution volume of the peripheral compartment, 54.4 mL/kg; and lag time, 0.633 minutes. The predictive performance of this model was better than that of the previous model.Conclusion: The PK parameters of landiolol were best described by a two-compartment model with lag time. Distribution volume of the central compartment and total body clearance of landiolol in patients with peripheral arterial disease were approximately 64% and 84% of those in healthy volunteers, respectively.

KW - Landiolol hydrochloride

KW - PAD

KW - Peripheral arterial disease

KW - Pharmacokinetic parameters

KW - Pharmacokinetics

KW - Target-controlled infusion

KW - TCI

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