caa a22 4500 475818261 CHVBK 20180406123815.0 cr unu---uuuuu 170329e20000401xx s 000 0 eng 10.1007/s002280050726 doi (NATIONALLICENCE)springer-10.1007/s002280050726 Pharmacokinetics and pharmacodynamics of propofol 6% SAZN versus propofol 1% SAZN and Diprivan-10 for short-term sedation following coronary artery bypass surgery [Elektronische Daten] [C. A. J. Knibbe, L. P. H. J. Aarts, P. F. M. Kuks, H. -J. Voortman, L. Lie-A-Huen, L. J. Bras, M. Danhof] Objective: A new formulation of propofol 6% in Lipofundin MCT/LCT 10% (propofol 6% SAZN) has been developed in order to reduce the fat, emulsifier and volume load that is given during prolonged infusions of propofol. The pharmacokinetics, pharmacodynamics and safety characteristics of propofol 6% SAZN were investigated during a short-term infusion and compared with the commercially available product propofol 1% in Intralipid 10% (Diprivan-10) and propofol 1% in Lipofundin MCT/LCT 10% (propofol 1% SAZN). Methods: In a randomised double-blind study, 24 male patients received a 5-h infusion of propofol at the rate of 1 mg/kg/h for sedation in the immediate postoperative period following coronary artery bypass surgery. Results: The average pharmacokinetic parameter estimates of clearance (Cl), volume of distribution at steady state (Vd,ss), elimination half-life (t 1/2,β) and distribution half-life (t 1/2,α) observed in the three groups were 28 ± 1.1 ml/kg/min, 1.8 ± 0.12 l/kg, 94 ± 4.1 min and 3.1 ± 0.26 min, respectively (mean ± SEM, n=24) and no significant differences were noted between the three formulations (P > 0.05). In one patient receiving propofol 6% SAZN, in two patients receiving propofol 1% SAZN and in three patients receiving Diprivan-10, the level of sedation was inadequate and additional sedative medication had to be given. In all other 18 patients, the level of sedation was adequate. The mean propofol concentration in these six inadequately sedated patients was lower than the adequately sedated patients (P=0.015). The serum triglyceride concentrations were not significantly different between the groups studied. No adverse events occurred in any of the patients. Conclusions: The pharmacokinetics, pharmacodynamics and safety characteristics of propofol 6% SAZN are in good agreement with those of the 1% formulations. Propofol 6% SAZN therefore provides a useful alternative to the commercially available 1% formulation for short-term sedation in the intensive care unit. Expected advantages in long-term sedation of the 6% over 1% formulation are the subject of an ongoing study. Springer-Verlag Berlin Heidelberg, 2000 Key words Anaesthetics i.v nationallicence Propofol nationallicence Pharmacokinetics nationallicence Knibbe C. A. J. Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein, The Netherlands e-mail: knibhoef@worldonline.nl Tel.: +31-30-6092612; Fax: +31-30-6093080, NL aut Aarts L. P. H. J. Department of Anaesthesiology and Intensive Care, St. Antonius Hospital, Nieuwegein, The Netherlands, NL aut Kuks P. F. M. Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein, The Netherlands e-mail: knibhoef@worldonline.nl Tel.: +31-30-6092612; Fax: +31-30-6093080, NL aut Voortman H. -J Department of Anaesthesiology and Intensive Care, St. Antonius Hospital, Nieuwegein, The Netherlands, NL aut Lie-A-Huen L. Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein, The Netherlands e-mail: knibhoef@worldonline.nl Tel.: +31-30-6092612; Fax: +31-30-6093080, NL aut Bras L. J. Department of Anaesthesiology and Intensive Care, St. Antonius Hospital, Nieuwegein, The Netherlands, NL aut Danhof M. Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, University of Leiden, Leiden, The Netherlands, NL aut https://doi.org/10.1007/s002280050726 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050726 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Knibbe C. A. J. Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein, The Netherlands e-mail: knibhoef@worldonline.nl Tel.: +31-30-6092612; Fax: +31-30-6093080, NL aut NATIONALLICENCE 700 1- Aarts L. P. H. J. Department of Anaesthesiology and Intensive Care, St. Antonius Hospital, Nieuwegein, The Netherlands, NL aut NATIONALLICENCE 700 1- Kuks P. F. M. Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein, The Netherlands e-mail: knibhoef@worldonline.nl Tel.: +31-30-6092612; Fax: +31-30-6093080, NL aut NATIONALLICENCE 700 1- Voortman H. -J Department of Anaesthesiology and Intensive Care, St. Antonius Hospital, Nieuwegein, The Netherlands, NL aut NATIONALLICENCE 700 1- Lie-A-Huen L. Department of Clinical Pharmacy, St. Antonius Hospital, P.O. Box 2500, 3430 EM Nieuwegein, The Netherlands e-mail: knibhoef@worldonline.nl Tel.: +31-30-6092612; Fax: +31-30-6093080, NL aut NATIONALLICENCE 700 1- Bras L. J. Department of Anaesthesiology and Intensive Care, St. Antonius Hospital, Nieuwegein, The Netherlands, NL aut NATIONALLICENCE 700 1- Danhof M. Leiden/Amsterdam Center for Drug Research, Division of Pharmacology, University of Leiden, Leiden, The Netherlands, NL aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer