Byung-Moon Choi1, Hyun-Gu Lee2, Hyo-Jin Byon3, Soo-Han Lee4, Eun-Kyung Lee5, Hee-Soo Kim6, Gyu-Jeong Noh1, 4
1 Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap 2-dong, Songpa-gu, Seoul, 138-736, Korea
2 University of Ulsan College of Medicine, Seoul, Korea
3 Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea
4 Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
5 Department of Statistics, Ewha Womans University, Seoul, Korea
6 Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea
Abstract
There have been no pharmacokinetic parameters and blood?brain equilibration rate constant (ke0) of propofol obtained in a single population of children, by which propofol can be administered using a target effect-site concentration controlled infusion. Thirty-nine, American Society of Anesthesiologists Physical Status 1-2 children aged 2-12 years were given an intravenous bolus of propofol (3 mg kg-1), followed by infusion (200 μg kg-1 min-1). Arterial drug concentrations and bispectral index (BIS) values were measured. Population pharmacokinetic and pharmacodynamic analysis was performed using nonlinear mixed effects modeling. External model validation was performed in a separate population of children. A two-compartment model and a sigmoid Emax model directly linked by an effect compartment well described the time courses of propofol concentration and BIS. The estimates of parameters were: V 1 (L) = 1.69, V 2 (L) = 27.2 + 0.929 × (weight - 25), Cl (L min-1) = 0.893 × (weight/23.6)0.966, Q (L min-1) = 1.3; E 0v = 76.9; E max = 35.4, Ce 50 (μg mL-1) = 3.47 - (0.095 × age) - (1.63 × mean infusion rate of remifentanil in μg kg-1 min-1); γ = 2.1; and k e0 (min-1) = 0.371. Pooled biases (95 % CI) of the target effect-site concentration controlled infusion system of propofol was -20.2 % (-23.3 to -18.1 %) and pooled inaccuracy was 30.4 % (28.6-32.7 %). Pooled biases of BIS prediction was -6.8 % (-9.1 to -4.1 %) and pooled inaccuracies was 19.1 % (17.5-20.9 %).The altered weight-based dose requirements of propofol are well described pharmacokinetically, and pharmacodynamically. Predictive performances of the TCI system in this study were clinically acceptable.
Keywords : Propofol, Pharmacokinetics, Pharmacodynamics