Propofol metabolism is enhanced after repetitive ketamine administration in rats: the role of cytochrome P-450 2B induction W.-H. Chan, T.-L. Chen, R.-M.

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Presentation transcript:

Propofol metabolism is enhanced after repetitive ketamine administration in rats: the role of cytochrome P-450 2B induction W.-H. Chan, T.-L. Chen, R.-M. Chen, W.-Z. Sun, T.-H. Ueng British Journal of Anaesthesia Volume 97, Issue 3, Pages 351-358 (September 2006) DOI: 10.1093/bja/ael173 Copyright © 2006 British Journal of Anaesthesia Terms and Conditions

Fig 1 The induction of hepatic P-450 2B by ketamine in rats. (a) P-450 2B-dependent PROD activity (pmol resorufin min−1 mg protein−1). The increase in PROD activity after ketamine pretreatment was reversed by the addition of orphenadrine, a P-450 2B inhibitor. *Value was significantly different from the control by anova followed by Dunnett test, P<0.05. Ctrl: control; Ket: ketamine; Orph: orphenadrine. Each bar represents mean and se. (b) Immunoblot of P-450 2B1/2 proteins. (c) Semi-quantitative RT–PCR analysis P-450 2B1/2 and cyclophilin mRNA. Each group consisted of three animals in PROD and immunoblot experiments and four animals in the RT–PCR analysis experiment. British Journal of Anaesthesia 2006 97, 351-358DOI: (10.1093/bja/ael173) Copyright © 2006 British Journal of Anaesthesia Terms and Conditions

Fig 2 The effect of ketamine pretreatment on residual propofol concentration after incubation with rat hepatic microsomes. (a) Solid bar: microsomes from the control rats; hatched bar: microsomes from rats with ketamine pretreatment in absence and presence of orphenadrine. Each bar represents mean and se. (b) Inhibition of PROD activity (pmol resorufin min−1 mg protein−1) by orphenadrine in microsomes from ketamine-pretreated rats. Each point represents mean and se. Data were analysed by anova followed by Dunnett test to compare with the control group. There were three animals per group. *Value was significantly different from the control, P<0.05. British Journal of Anaesthesia 2006 97, 351-358DOI: (10.1093/bja/ael173) Copyright © 2006 British Journal of Anaesthesia Terms and Conditions

Fig 3 The effect of ketamine (Ket) and orphenadrine (Orph) pretreatment on propofol sleeping time in rats. Each bar represents mean and se. Data were analysed by anova followed by Dunnett test for comparison to the control (Ctrl) group. The control group comprised four animals and each treatment comprised three animals. *Value was significantly different from the control, P<0.05. British Journal of Anaesthesia 2006 97, 351-358DOI: (10.1093/bja/ael173) Copyright © 2006 British Journal of Anaesthesia Terms and Conditions

Fig 4 The effect of ketamine pretreatment on whole blood propofol concentration in rats (log mg litre−1). Filled circle: control group; open circle: ketamine-pretreated group. Each point represents mean and se. *Value was significantly different from respective control groups, P<0.05. Each group comprised three animals. British Journal of Anaesthesia 2006 97, 351-358DOI: (10.1093/bja/ael173) Copyright © 2006 British Journal of Anaesthesia Terms and Conditions