T. Iirola, H. Ihmsen, R. Laitio, E. Kentala, R. Aantaa, J. -P

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Population pharmacokinetics of dexmedetomidine during long-term sedation in intensive care patients T. Iirola, H. Ihmsen, R. Laitio, E. Kentala, R. Aantaa, J.-P. Kurvinen, M. Scheinin, H. Schwilden, J. Schüttler, K.T. Olkkola British Journal of Anaesthesia Volume 108, Issue 3, Pages 460-468 (March 2012) DOI: 10.1093/bja/aer441 Copyright © 2012 The Author(s) Terms and Conditions

Fig 1 Time courses of the measured dexmedetomidine concentrations. Each line represents one subject. British Journal of Anaesthesia 2012 108, 460-468DOI: (10.1093/bja/aer441) Copyright © 2012 The Author(s) Terms and Conditions

Fig 2 Baseline-normalized relative CO (baseline=1) vs measured dexmedetomidine concentration. The solid black line shows the prediction of the sigmoid model, fitted to the data. British Journal of Anaesthesia 2012 108, 460-468DOI: (10.1093/bja/aer441) Copyright © 2012 The Author(s) Terms and Conditions

Fig 3 Scatter plots of the individual Bayesian estimates of clearance vs age (a) and of volume of distribution at steady-state vs albumin concentration (b). Each data point represents one subject. In four subjects, no albumin concentrations were available. Multiple albumin concentration measurements within one subject were averaged. The solid black line was obtained by linear regression analysis; R2 is the corresponding regression coefficient. British Journal of Anaesthesia 2012 108, 460-468DOI: (10.1093/bja/aer441) Copyright © 2012 The Author(s) Terms and Conditions

Fig 4 Measured dexmedetomidine concentrations vs the individual Bayesian predictions (a) and the population predictions (b), as obtained with the final pharmacokinetic model. The solid black line is the line of identity (measured=predicted). British Journal of Anaesthesia 2012 108, 460-468DOI: (10.1093/bja/aer441) Copyright © 2012 The Author(s) Terms and Conditions

Fig 5 Simulations of the time for a 50% concentration decrement after termination of a continuous drug infusion (context-sensitive half-time) for fictive subjects having (a) different age and an equal plasma albumin concentration of 14 g litre−1, and (b) different albumin concentration and an equal age of 60 yr (Table 3). British Journal of Anaesthesia 2012 108, 460-468DOI: (10.1093/bja/aer441) Copyright © 2012 The Author(s) Terms and Conditions

Fig 6 Simulations of the time for a 50% concentration decrement after termination of a continuous drug infusion (context-sensitive half-time) for a typical subject of this study (age: 60 yr, albumin concentration: 14 g litre−1, height: 174 cm) using the pharmacokinetic models of this study and of the studies by Lin and colleagues,10 Dyck and colleagues,9 Talke and colleagues,11 and Venn and colleagues.3 British Journal of Anaesthesia 2012 108, 460-468DOI: (10.1093/bja/aer441) Copyright © 2012 The Author(s) Terms and Conditions

Fig 7 Time courses of heart rate (a) and of systolic (dark blue) and diastolic (light blue) arterial pressure during dexmedetomidine infusion (b). Data are shown as mean (sd). British Journal of Anaesthesia 2012 108, 460-468DOI: (10.1093/bja/aer441) Copyright © 2012 The Author(s) Terms and Conditions