Population pharmacokinetic and pharmacodynamic model of propofol externally validated in children.
There have been no pharmacokinetic parameters and blood-brain equilibration rate constant (k e0) 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 E max 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 0 = 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.
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.
Byung-Moon
BM
Choi
Hyun-Gu
HG
Lee
Hyo-Jin
HJ
Byon
Soo-Han
SH
Lee
Eun-Kyung
EK
Lee
Hee-Soo
HS
Kim
Gyu-Jeong
GJ
Noh
D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous / Q000379:methods; D007275:Injections, Intravenous / Q000379:methods; D008297:Male; D008954:Models, Biological; D010880:Piperidines / Q000008:administration & dosage / Q000493:pharmacokinetics; D015742:Propofol / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000077208:Remifentanil
D018686:Anesthetics, Intravenous; D010880:Piperidines; D000077208:Remifentanil; D015742:Propofol