Population Pharmacokinetic and Pharmacodynamic Modeling of Microemulsion Propofol in Healthy Volunteers: Comparison With Lipid Emulsion Propofol

The Subjects fasted for 6 h before study drug administration. An 18-gauge angiocatheter was placed in a vein of the antecubital area. A second angiocatheter was placed in the contralateral radial artery for frequent blood sampling. Subjects were monitored with electrocardiography, pulse oximetry, end-tidal carbon dioxide concentration, and invasive blood pressure measurement (Datex-Ohmeda S/5;Planar Systems, Inc., Beaverton, OR) and Bispectral Index (BIS) (Aspect 2000; Aspect Medical Systems, Inc., Newton,MA). In addition, the electroencephalographic activity of seven monopolar channels (Fp1, Fp2, F3, F4, Cz, P3, and P4, referenced by A2) was recorded by QEEG-8 (LXE3208, Laxtha Inc., Daejeon, Korea).

The subjects were stratified into three age groups (19-40, 41-64, and > 65 yr), and each group included 10 male and 10 female volunteers. Each subject received both propofol formulations in a crossover fashion separated by a 7-day washout period, and the order of the drug administration was randomized. Subjects received both propofol formulations during 60 min. The infusion rate was assigned according to a nonblinded, randomized design to 1.5, 3, 6, or 12 mg/kg/hr.

Samples were collected in ethylenediaminetetraacetic acid (EDTA) tube and centrifuged for 10 min at 3,500rpm. Plasma was stored at -70°C until assay. Arterial blood samples (4 ml) were taken at preset intervals: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 15, 20, 30, 40, 50, 58, 60, 62, 66, 70, 80, 90, 120 and 150 min after administration of propofol. Venous blood samples (4ml) were taken at preset intervals: 180, 240, 300, 600, 720 and 1,200 min after administration of propofol. In addition, arterial samples were drawn when LOC (loss of consciousness) and ROC (recovery of consciousness) were observed.