Disposition of Propofol Administered as Constant Rate Intravenous Infusions in Humans
- 1 December 1987
- journal article
- research article
- Published by Wolters Kluwer Health in Anesthesia & Analgesia
- Vol. 66 (12) , 1256-1263
- https://doi.org/10.1213/00000539-198712000-00010
Abstract
The disposition of the intravenous anesthetic propofol was studied when administered as a constant rate infusion at 3, 6, and 9 mg .cntdot. kg-1 .cntdot. hr-1 for at least 2 hr to three groups of six patients each undergoing surgery under regional anesthesia. Arterial blood samples were collected at selected times during and up to 8 hr after infusion. Whole blood propofol concentrations were determined by high-performance liquid chromatography with fluorescence detection. Using a non-linear least-squares regression analysis, the individual data sets were best fitted by a three-compartment open mamillary model with central elimination in 17 patients. In one patient a biexponential equation was more appropriate. Derived pharmacokinetic parameters expressed as mean values .+-. SD indicated an initial fast distribution (t1/2.pi.; 2.8 .+-. 1.2 min), with an intermediate phase (t1/2.alpha.; 31.4 .+-. 14.7 min), and a long terminal phase (t1/2.beta.; 335 .+-. 227 min), a large volume of distribution at steady state (Vss, 287 .+-. 213 L), and a high blood clearance (Clb, 1.7 .+-. 0.3 L/min). The fraction of drug in the central compartment in the terminal phase was low (Fc, 0.02). The elimination rate constant (K10, 0.1190 .+-. 0.0351 min-1) was large compared with the other transfer rate constants and was responsible for the large amount of drug eliminated during distribution. The fraction of drug eliminated during the terminal phase amounted to 0.28. The slow return of drug from remote tissues (K31, 0.0033 .+-. 0.0013 min-1) was rate limiting in the ultimate elimination. After 120 min of infusion, 85 .+-. 15% of the predicted concentration at steady state (Css) was obtained; Css was linearly related to the infusion rate. The pharmacokinetic profile of propofol appeared linear over the dosage range studied.This publication has 7 references indexed in Scilit:
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