caa a22 4500 605534195 CHVBK 20210128100841.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s10928-015-9408-2 doi (NATIONALLICENCE)springer-10.1007/s10928-015-9408-2 Population pharmacokinetic and pharmacodynamic model of propofol externally validated in children [Elektronische Daten] [Byung-Moon Choi, Hyun-Gu Lee, Hyo-Jin Byon, Soo-Han Lee, Eun-Kyung Lee, Hee-Soo Kim, Gyu-Jeong Noh] 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 2-12years were given an intravenous bolus of propofol (3mgkg−1), followed by infusion (200µgkg−1min−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 (Lmin−1)=0.893×(weight/23.6)0.966, Q (Lmin−1)=1.3; E 0=76.9; E max =35.4, Ce 50 (μgmL−1)=3.47−(0.095×age)−(1.63×mean infusion rate of remifentanil in µgkg−1min−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. Springer Science+Business Media New York, 2015 Propofol nationallicence Pharmacokinetics nationallicence Pharmacodynamics nationallicence Choi Byung-Moon Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap 2-dong, Songpa-gu, 138-736, Seoul, Korea aut Lee Hyun-Gu University of Ulsan College of Medicine, Seoul, Korea aut Byon Hyo-Jin Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea aut Lee Soo-Han Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea aut Lee Eun-Kyung Department of Statistics, Ewha Womans University, Seoul, Korea aut Kim Hee-Soo Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, 110-744, Seoul, Korea aut Noh Gyu-Jeong Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap 2-dong, Songpa-gu, 138-736, Seoul, Korea aut Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/2(2015-04-01), 163-177 1567-567X 42:2<163 2015 42 10928 https://doi.org/10.1007/s10928-015-9408-2 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10928-015-9408-2 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Choi Byung-Moon Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap 2-dong, Songpa-gu, 138-736, Seoul, Korea aut NATIONALLICENCE 700 1- Lee Hyun-Gu University of Ulsan College of Medicine, Seoul, Korea aut NATIONALLICENCE 700 1- Byon Hyo-Jin Department of Anesthesiology and Pain Medicine, Yonsei University College of Medicine, Seoul, Korea aut NATIONALLICENCE 700 1- Lee Soo-Han Department of Clinical Pharmacology and Therapeutics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea aut NATIONALLICENCE 700 1- Lee Eun-Kyung Department of Statistics, Ewha Womans University, Seoul, Korea aut NATIONALLICENCE 700 1- Kim Hee-Soo Department of Anesthesiology and Pain Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, 110-744, Seoul, Korea aut NATIONALLICENCE 700 1- Noh Gyu-Jeong Department of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, 388-1 Pungnap 2-dong, Songpa-gu, 138-736, Seoul, Korea aut NATIONALLICENCE 773 0- Journal of Pharmacokinetics and Pharmacodynamics Springer US; http://www.springer-ny.com 42/2(2015-04-01), 163-177 1567-567X 42:2<163 2015 42 10928