Population pharmacokinetic and pharmacodynamic model of propofol externally validated in children
There have been no pharmacokinetic parameters and blood–brain equilibration rate constant ( k e 0 ) 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 Anesthesio...
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Veröffentlicht in: | Journal of pharmacokinetics and pharmacodynamics 2015-04, Vol.42 (2), p.163-177 |
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Sprache: | eng |
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Zusammenfassung: | There have been no pharmacokinetic parameters and blood–brain equilibration rate constant (
k
e
0
) 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
e
0
(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. |
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ISSN: | 1567-567X 1573-8744 |
DOI: | 10.1007/s10928-015-9408-2 |