Concurrent ketamine and alfentanil administration: pharmacokinetic considerations.
BACKGROUND
A ketamine-alfentanil combination has been suggested for total i.v. anaesthesia. We determined the pharmacokinetics of ketamine and alfentanil, alone and together, in three groups of adult male rats, to assess any pharmacokinetic interaction.


METHODS
Group 1 animals were infused with i.v. ketamine for 5 min; in group 2, constant low plasma concentrations of alfentanil were maintained by computer-controlled infusion; in group 3, the treatments were combined. Serial plasma and terminal tissue concentrations were measured by high performance liquid chromatography or gas chromatography-mass spectrometry.


RESULTS
In the presence of alfentanil, the mean plasma ketamine concentration-time area under the curve (AUC) value was significantly lower (by 13%, P<0.05), while clearance (CIT) and volume of distribution (Vss) were significantly higher (by 16 and 28%, respectively, both P<0.05). Tissue:plasma distribution coefficients for ketamine in the presence of alfentanil were significantly higher in forebrain (by 128%, P<0.005), hindbrain (by 207%, P<0.01), gut (by 254%, P<0.005), and fat (by 344%, P<0.0001). Mean AUC values for alfentanil did not differ significantly in the presence of ketamine, but alfentanil tissue concentrations were significantly lower in forebrain (by 77%, P<0.0001), hindbrain (by 28%, P<0.01), heart (by 33%, P<0.01), lung (30%, P<0.05), and gut (by 21%, P<0.05). Corresponding tissue:plasma distribution coefficients were significantly lower for forebrain (by 69%, P<0.0001) alone.


CONCLUSIONS
The finding that the distribution of ketamine into the brain was increased by low plasma concentrations of alfentanil could have important clinical applications for pain management.
Edwards
S R
SR
Centre for Anaesthesia and Pain Management Research, University of Sydney at Royal North Shore Hospital, St Leonards, NSW, Australia.
Minto
C F
CF
Mather
L E
LE
D015760:Alfentanil / Q000097:blood / Q000493:pharmacokinetics*; D000771:Anesthesia, Intravenous / Q000379:methods; D019162:Anesthetics, Combined / Q000097:blood / Q000493:pharmacokinetics*; D000778:Anesthetics, Dissociative / Q000097:blood / Q000493:pharmacokinetics*; D018686:Anesthetics, Intravenous / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D007649:Ketamine / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
D019162:Anesthetics, Combined; D000778:Anesthetics, Dissociative; D018686:Anesthetics, Intravenous; D015760:Alfentanil; D007649:Ketamine