3
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          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.

          Related collections

          Most cited references 15

          • Record: found
          • Abstract: found
          • Article: not found

          Influence of age and gender on the pharmacokinetics and pharmacodynamics of remifentanil. I. Model development.

          Previous studies have reported conflicting results concerning the influence of age and gender on the pharmacokinetics and pharmacodynamics of fentanyl, alfentanil, and sufentanil. The aim of this study was to determine the influence of age and gender on the pharmacokinetics and pharmacodynamics of the new short-acting opioid remifentanil. Sixty-five healthy adults (38 men and 27 women) ages 20 to 85 y received remifentanil by constant-rate infusion of 1 to 8 micrograms.kg-1.min-1 for 4 to 20 min. Frequent arterial blood samples were drawn and assayed for remifentanil concentration. The electroencephalogram was used as a measure of drug effect. Population pharmacokinetic and pharmacodynamic modeling was performed using the software package NONMEM. The influence of volunteer covariates were analyzed using a generalized additive model. The performances of the simple (without covariates) and complex (with covariates) models were evaluated prospectively in an additional 15 healthy participants ages 41 to 84 y. The parameters for the simple three-compartment pharmacokinetic model were V1 = 4.98 l, V2 = 9.01 l, V3 = 6.54 l, Cl1 = 2.46 l/min, Cl2 = 1.69 l/min, and Cl3 = 0.065 l/min. Age and lean body mass were significant covariates. From the ages of 20 to 85 y, V1 and Cl1 decreased by approximately 25% and 33%, respectively. The parameters for the simple sigmoid Emax pharmacodynamic model were Ke0 = 0.516 min-1, E0 = 20 Hz, Emax = 5.62 Hz, EC50 = 11.2 ng/ml, and gamma = 2.51. Age was a significant covariate of EC50 and Ke0, with both decreasing by approximately 50% for the age range studied. The complex pharmacokinetic-pharmacodynamic model performed better than did the simple model when applied prospectively. This study identified (1) an effect of age on the pharmacokinetics and pharmacodynamics of remifentanil; (2) an effect of lean body mass on the pharmacokinetic parameters; and (3) no influence of gender on any pharmacokinetic or pharmacodynamic parameter.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Conditional weighted residuals (CWRES): a model diagnostic for the FOCE method.

            Population model analyses have shifted from using the first order (FO) to the first-order with conditional estimation (FOCE) approximation to the true model. However, the weighted residuals (WRES), a common diagnostic tool used to test for model misspecification, are calculated using the FO approximation. Utilizing WRES with the FOCE method may lead to misguided model development/evaluation. We present a new diagnostic tool, the conditional weighted residuals (CWRES), which are calculated based on the FOCE approximation. CWRES are calculated as the FOCE approximated difference between an individual's data and the model prediction of that data divided by the root of the covariance of the data given the model. Using real and simulated data the CWRES distributions behave as theoretically expected under the correct model. In contrast, in certain circumstances, the WRES have distributions that greatly deviate from the expected, falsely indicating model misspecification. CWRES/WRES comparisons can also indicate if the FOCE estimation method will improve the results of an FO model fit to data. Utilization of CWRES could improve model development and evaluation and give a more accurate picture of if and when a model is misspecified when using the FO or FOCE methods.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Development of a highly cardioselective ultra short-acting beta-blocker, ONO-1101.

              A novel, highly cardioselective ultra short-acting beta-blocker, ONO-1101, has been developed for application in the emergency treatment of tachycardia and better control of heart rate in surgery. This agent is approximately nine times more potent in beta-blocking activity in vivo and eight times more cardioselective in vitro than esmolol. This beta-blocking drug has a short duration of activity, enabling rapid recovery after cessation of administration if side effects occur. It can be used safely in patients suffering from acute heart disease and represents a major therapeutic advance in the treatment of heart disease.
                Bookmark

                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2015
                17 January 2015
                : 11
                : 107-114
                Affiliations
                [1 ]Surgical Operation Department, Asahikawa Medical University Hospital, Asahikawa, Japan
                [2 ]Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, Asahikawa, Japan
                [3 ]Department of Oncology Pharmaceutical Care and Sciences, Okayama University, Okayama, Japan
                [4 ]Pharmacokinetic Research Laboratories, Ono Pharmaceutical Co., Ltd., Osaka, Japan
                [5 ]Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical University, Asahikawa, Japan
                Author notes
                Correspondence: Takayuki Kunisawa, Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido 0788510, Japan, Tel +81 166 68 2583, Fax +81 166 68 2589, Email taka.kunisawa@ 123456nifty.ne.jp
                Article
                tcrm-11-107
                10.2147/TCRM.S74867
                4303402
                © 2015 Kunisawa et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Comments

                Comment on this article