PMID- 16845130
OWN - NLM
STAT- MEDLINE
DCOM- 20061010
LR  - 20180126
IS  - 0007-0912 (Print)
IS  - 0007-0912 (Linking)
VI  - 97
IP  - 3
DP  - 2006 Sep
TI  - Propofol metabolism is enhanced after repetitive ketamine administration in rats: 
      the role of cytochrome P-450 2B induction.
PG  - 351-8
AB  - BACKGROUND: In a series of ex vivo and in vivo studies we investigated the 
      ability of repetitive ketamine administration to alter the metabolism and 
      anaesthetic effect of propofol and the role of ketamine-mediated P-450 2B 
      induction in rats. METHODS: Male Wistar rats were pretreated with 80 mg kg(-1) 
      ketamine i.p. twice daily for 4 days. Pentoxyresorufin O-dealkylation (PROD), 
      P-450 2B protein and mRNA were determined. Residual propofol concentration was 
      measured after incubating hepatic microsomes with 100 muM propofol. Sleeping 
      times induced by i.p. 80 mg kg(-1) propofol were determined. Orphenadrine, a 
      P-450 2B inhibitor, was added in both ex vivo and in vivo studies. Finally, 
      serial whole blood propofol concentrations were determined after i.v. infusion of 
      15 mg kg(-1) propofol. RESULTS: Ketamine pretreatment produced 5.4-, 3.4- and 
      1.7-fold increases in hepatic PROD activity, P-450 2B protein and mRNA, 
      respectively. Residual propofol concentration was 46% lower after incubation with 
      microsomes from ketamine-pretreated rats than in the control group. The addition 
      of orphenadrine to ketamine-pretreated microsomes produced an increase in 
      residual propofol concentration in a concentration-dependent manner. Ketamine 
      pretreatment reduced propofol sleeping time to 12% of the control, which was 
      reversed by orphenadrine. The whole blood propofol concentration in 
      ketamine-pretreated rats was significantly lower than that of control rats at 1, 
      2, 4 and 8 min after cessation of propofol infusion. CONCLUSIONS: Repetitive 
      ketamine administration enhances propofol metabolism and reduces propofol 
      sleeping time in rats. We suggest that P-450 2B induction may produce 
      ketamine-propofol interaction in anaesthetic practice.
FAU - Chan, W-H
AU  - Chan WH
AD  - Institute of Toxicology, College of Medicine, National Taiwan University 1 Jen-Ai 
      Road, Section 1, Taipei, Taiwan.
FAU - Chen, T-L
AU  - Chen TL
FAU - Chen, R-M
AU  - Chen RM
FAU - Sun, W-Z
AU  - Sun WZ
FAU - Ueng, T-H
AU  - Ueng TH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060715
PL  - England
TA  - Br J Anaesth
JT  - British journal of anaesthesia
JID - 0372541
RN  - 0 (Anesthetics, Combined)
RN  - 0 (Anesthetics, Dissociative)
RN  - 0 (Anesthetics, Intravenous)
RN  - 0 (Enzyme Inhibitors)
RN  - 690G0D6V8H (Ketamine)
RN  - AL805O9OG9 (Orphenadrine)
RN  - EC 1.14.- (Steroid Hydroxylases)
RN  - EC 1.14.14.1 (Aryl Hydrocarbon Hydroxylases)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP2B1)
RN  - EC 1.14.14.1 (steroid 16-beta-hydroxylase)
RN  - YI7VU623SF (Propofol)
SB  - IM
MH  - Anesthetics, Combined/pharmacology
MH  - Anesthetics, Dissociative/pharmacology
MH  - Anesthetics, Intravenous/blood/*pharmacokinetics
MH  - Animals
MH  - Aryl Hydrocarbon Hydroxylases/antagonists & inhibitors/*physiology
MH  - Cytochrome P-450 CYP2B1/antagonists & inhibitors/*physiology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Ketamine/*pharmacology
MH  - Male
MH  - Microsomes, Liver/metabolism
MH  - Orphenadrine/pharmacology
MH  - Propofol/blood/*pharmacokinetics
MH  - Rats
MH  - Rats, Wistar
MH  - Steroid Hydroxylases/antagonists & inhibitors/*physiology
EDAT- 2006/07/18 09:00
MHDA- 2006/10/13 09:00
CRDT- 2006/07/18 09:00
PHST- 2006/07/18 09:00 [pubmed]
PHST- 2006/10/13 09:00 [medline]
PHST- 2006/07/18 09:00 [entrez]
AID - S0007-0912(17)35436-3 [pii]
AID - 10.1093/bja/ael173 [doi]
PST - ppublish
SO  - Br J Anaesth. 2006 Sep;97(3):351-8. doi: 10.1093/bja/ael173. Epub 2006 Jul 15.