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Population pharmacokinetic analysis of propofol in underweight patients under general anaesthesia

Title
Population pharmacokinetic analysis of propofol in underweight patients under general anaesthesia
Authors
Park, J. H.Choi, S. M.Lee, K. H.Yun, H. J.Lee, E. K.Choi, B. M.Noh, G. J.
Ewha Authors
이은경
SCOPUS Author ID
이은경scopus
Issue Date
2018
Journal Title
BRITISH JOURNAL OF ANAESTHESIA
ISSN
0007-0912JCR Link

1471-6771JCR Link
Citation
BRITISH JOURNAL OF ANAESTHESIA vol. 121, no. 3, pp. 559 - 566
Keywords
pharmacokineticspropofolunderweight
Publisher
ELSEVIER SCI LTD
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
Abstract
Background: The modified Marsh and Schnider pharmacokinetic models for propofol consistently produce negatively and positively biased predictions in underweight patients, respectively. We aimed to develop a new pharmacokinetic model of propofol in underweight patients. Methods: Twenty underweight (BMI<18.5 kg m(-2)) patients aged 20-68 yr were given an i.v. bolus of propofol (2 mg kg(-1)) for induction of anaesthesia. Anaesthesia was maintained with a zero-order infusion (8 mg kg(-1) h(-1)) of propofol and target-controlled infusion of remifentanil. Arterial blood was sampled at preset intervals. A population pharmacokinetic analysis was performed using non-linear mixed effects modelling. The time to peak effect (t(peak), maximally reduced bispectral index) was measured in 28 additional underweight patients receiving propofol 2 mg kg(-1). Results: In total, 455 plasma concentration measurements from the 20 patients were used to characterise the pharmacokinetics of propofol. A three-compartment mammillary model well described the propofol concentration time course. BMI and lean body mass (LBM) calculated using the Janmahasatian formula were significant covariates for the rapid peripheral volume of distribution and for the clearance of the final pharmacokinetic model of propofol, respectively. The parameter estimates were as follows: V-1(L)=2.02, V-2(L)=12.9((BMI/18.5)), V-3(L)=139, Cl (L.min(-1))=1.66((LBM/40)), (L.min(-1))=1.44, Q(2) (L.min(-1))=0.87+0.0189x(LBM-40). The median t(peak) of propofol was 1.32 min (n=48). Conclusions: A three-compartment mammillary model can be used to administer propofol via target effect-site con- centration-controlled infusion of propofol in underweight patients.
DOI
10.1016/j.bja.2018.04.045
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자연과학대학 > 통계학전공 > Journal papers
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