Population pharmacokinetic and pharmacodynamic model of propofol externally validated in children

Byung Moon Choi, Hyun Gu Lee, Hyo Jin Byon, Soo Han Lee, Eun Kyung Lee, Hee Soo Kim, Gyu Jeong Noh

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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: V1 (L) = 1.69, V2 (L) = 27.2 + 0.929 × (weight − 25), Cl (L min−1) = 0.893 × (weight/23.6)0.966, Q (L min−1) = 1.3; E0 = 76.9; Emax = 35.4, Ce50 (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 ke0 (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.

Original languageEnglish
Pages (from-to)163-177
Number of pages15
JournalJournal of Pharmacokinetics and Pharmacodynamics
Volume42
Issue number2
DOIs
StatePublished - 11 Mar 2015

Bibliographical note

Funding Information:
We are grateful to In-Jin Jang, M.D. and Kyung-Sang Yu, M.D. from the Clinical Research Center of Seoul National University (Seoul, Korea) for measuring plasma concentrations of propofol. This work was supported by the Seoul National University Hospital Research Fund (0420100190, 0420110910) of Seoul National University Hospital and the Student Research Grant (11-12) of University of Ulsan College of Medicine, Seoul, Korea.

Publisher Copyright:
© 2015, Springer Science+Business Media New York.

Keywords

  • Pharmacodynamics
  • Pharmacokinetics
  • Propofol

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