Early Phase Pharmacokinetics but Not Pharmacodynamics Are Influenced by Propofol Infusion Rate
-
- Kenichi Masui
- * Assistant Professor, Department of Anesthesiology, National Defense Medical College, Tokorozawa, Japan and Research Fellow, Department of Anesthesia, Ghent University, Ghent, Belgium; † Assistant Professor, ‡ Professor and Chairman, Department of Anesthesiology, National Defense Medical College, Tokorozawa, Japan; § Lecturer, Department of Anesthesiology, Osaka University Graduate School of Med
-
- Marimo Kira
- * Assistant Professor, Department of Anesthesiology, National Defense Medical College, Tokorozawa, Japan and Research Fellow, Department of Anesthesia, Ghent University, Ghent, Belgium; † Assistant Professor, ‡ Professor and Chairman, Department of Anesthesiology, National Defense Medical College, Tokorozawa, Japan; § Lecturer, Department of Anesthesiology, Osaka University Graduate School of Med
-
- Tomiei Kazama
- * Assistant Professor, Department of Anesthesiology, National Defense Medical College, Tokorozawa, Japan and Research Fellow, Department of Anesthesia, Ghent University, Ghent, Belgium; † Assistant Professor, ‡ Professor and Chairman, Department of Anesthesiology, National Defense Medical College, Tokorozawa, Japan; § Lecturer, Department of Anesthesiology, Osaka University Graduate School of Med
-
- Satoshi Hagihira
- * Assistant Professor, Department of Anesthesiology, National Defense Medical College, Tokorozawa, Japan and Research Fellow, Department of Anesthesia, Ghent University, Ghent, Belgium; † Assistant Professor, ‡ Professor and Chairman, Department of Anesthesiology, National Defense Medical College, Tokorozawa, Japan; § Lecturer, Department of Anesthesiology, Osaka University Graduate School of Med
-
- Eric P. Mortier
- * Assistant Professor, Department of Anesthesiology, National Defense Medical College, Tokorozawa, Japan and Research Fellow, Department of Anesthesia, Ghent University, Ghent, Belgium; † Assistant Professor, ‡ Professor and Chairman, Department of Anesthesiology, National Defense Medical College, Tokorozawa, Japan; § Lecturer, Department of Anesthesiology, Osaka University Graduate School of Med
-
- Michel M. R. F. Struys
- * Assistant Professor, Department of Anesthesiology, National Defense Medical College, Tokorozawa, Japan and Research Fellow, Department of Anesthesia, Ghent University, Ghent, Belgium; † Assistant Professor, ‡ Professor and Chairman, Department of Anesthesiology, National Defense Medical College, Tokorozawa, Japan; § Lecturer, Department of Anesthesiology, Osaka University Graduate School of Med
説明
<jats:sec> <jats:title>Background</jats:title> <jats:p>Conventional compartmental pharmacokinetic models wrongly assume instantaneous drug mixing in the central compartment, resulting in a flawed prediction of drug disposition for the first minutes, and the flaw affects pharmacodynamic modeling. This study examined the influence of the administration rate and other covariates on early phase kinetics and dynamics of propofol by using the enlarged structural pharmacokinetic model.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Fifty patients were randomly assigned to one of five groups to receive 1.2 mg/kg propofol given with the rate of 10 to 160 mg . kg(-1). h(-1). Arterial blood samples were taken frequently, especially during the first minute. The authors compared four basic pharmacokinetic models by using presystemic compartments and the time shift of dosing, LAG time. They also examined a sigmoidal maximum possible drug effect pharmacodynamic model. Patient characteristics and dose rate were obtained to test the model structure.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>Our final pharmacokinetic model includes two conventional compartments enlarged with a LAG time and six presystemic compartments and includes following covariates: dose rate for transit rate constant, age for LAG time, and weight for central distribution volume. However, the equilibration rate constant between central and effect compartments was not influenced by infusion rate.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>This study found that a combined pharmacokinetic-dynamic model consisting of a two-compartmental model with a LAG time and presystemic compartments and a sigmoidal maximum possible drug effect model accurately described the early phase pharmacology of propofol during infusion rate between 10 and 160 mg . kg(-1). h(-1). The infusion rate has an influence on kinetics, but not dynamics. Age was a covariate for LAG time.</jats:p> </jats:sec>
収録刊行物
-
- Anesthesiology
-
Anesthesiology 111 (4), 805-817, 2009-10-01
Ovid Technologies (Wolters Kluwer Health)