Population pharmacokinetic and pharmacodynamic model of propofol externally validated in children

Journal of Pharmacokinetics and Pharmacodynamics
Byung-Moon ChoiGyu-Jeong Noh

Abstract

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 ...Continue Reading

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Citations

Oct 4, 2016·Clinical and Experimental Pharmacology & Physiology·SangMin ChoeGyu-Jeong Noh
Mar 29, 2019·Anesthesiology·Brian J Anderson, Oliver Bagshaw
Nov 15, 2016·Computational Intelligence and Neuroscience·Kyung-Jin YouHyun-Chool Shin
Oct 31, 2019·Anesthesia and Pain Medicine·Il DohGyu-Jeong Noh
Mar 6, 2021·Korean journal of anesthesiology·Byung-Moon Choi

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