title: Target-controlled infusion and population pharmacokinetics of landiolol hydrochloride in gynecologic patients.
abstract: OBJECTIVE
  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 (V 1) 74.9 mL/kg, inter-compartmental clearance (Q) 70.9 mL/min/kg, distribution volume of the peripheral compartment (V 2) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Surgical Operation Department, Asahikawa Medical University Hospital, Asahikawa, Japan, taka.kunisawa@nifty.ne.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kunisawa
authors.forename: Akio
authors.initials: A
authors.lastname: Yamagishi
authors.forename: Manabu
authors.initials: M
authors.lastname: Suno
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakade
authors.forename: Ryunosuke
authors.initials: R
authors.lastname: Higashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kurosawa
authors.forename: Ami
authors.initials: A
authors.lastname: Sugawara
authors.forename: Kazuo
authors.initials: K
authors.lastname: Matsubara
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwasaki
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000328:Adult; D000368:Aged; D044466:Asian People; D001794:Blood Pressure / Q000187:drug effects; D016503:Drug Delivery Systems; D005260:Female; D013509:Gynecologic Surgical Procedures / Q000379:methods*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D015233:Models, Statistical; D009025:Morpholines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019990:Perioperative Care; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D000319:Adrenergic beta-Antagonists; D009025:Morpholines; C077049:landiolol; D014508:Urea