F. Ravenelle, P. Vachon, A. E. Rigby-Jones, J. R. Sneyd, D

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Presentation transcript:

Anaesthetic effects of propofol polymeric micelle: a novel water soluble propofol formulation F. Ravenelle, P. Vachon, A.E. Rigby-Jones, J.R. Sneyd, D. Le Garrec, S. Gori, D. Lessard, D.C. Smith British Journal of Anaesthesia Volume 101, Issue 2, Pages 186-193 (August 2008) DOI: 10.1093/bja/aen147 Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 1 (a) Chemical structure and schematic representation of a poly(N-vinyl-2-pyrrolidone)-block-poly(d,l-lactide) (PVP-PLA) copolymer. Number of repeating units are distributions with number average values where n ≈ 22 and m ≈ 20. The dark grey segment of copolymer represents the water-soluble PVP moiety and the light grey segment represents the lipophilic PLA moiety. (b) Schematic representation of a propofol-loaded micelle of PVP-PLA (Propofol-PM) in solution above its critical micelle concentration (CMC ∼ 6 ppm) (left) and after injection and dilution below its CMC (right). British Journal of Anaesthesia 2008 101, 186-193DOI: (10.1093/bja/aen147) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 2 Average population pharmacokinetic model predicted profiles after a single dose of propofol 1%. British Journal of Anaesthesia 2008 101, 186-193DOI: (10.1093/bja/aen147) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 3 Plots demonstrating the performance of the final weight and drug administration adjusted pharmacokinetic model. (a) and (b) show the observed plasma concentration vs the population model predicted and individualized model predictions, respectively. These plots demonstrate the overall model goodness-of-fit. (c) shows the absolute values of the weighted residuals (approximating to sd units) for the individualized model (IWRES) vs the individualized predictions. (d) shows the weighted residuals (WRES) vs time (min). British Journal of Anaesthesia 2008 101, 186-193DOI: (10.1093/bja/aen147) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions

Fig 4 Time to return of paw withdrawal reflex, time of first movement and time of righting after a single i.v. dose of propofol 1% (10 mg kg−1) for over 1 min. Study formulations were Diprivan® 1%, and aqueous solutions 1% reconstituted from Propofol-PM 7, 10, and 12%. The median is indicated by a thick horizontal line near the centre of the box. The edges of the boxes show the scores at the 25th and 75th percentiles. The box length shows the interquartile range (IQR). The whiskers show the range of values that fall within 1.5 IQR of the box. Values plotted with a ○ are more than 1.5 IQR outside the box, while extreme values plotted with a * are more than 3 IQR from the box. British Journal of Anaesthesia 2008 101, 186-193DOI: (10.1093/bja/aen147) Copyright © 2008 British Journal of Anaesthesia Terms and Conditions