date, the incidence of this polymorphism in canine breeds other than Beagles has
not been reported.
2.1.5 Cytochrome P450 2B11 in Dogs
The pharmacokinetic disposition of some drugs is markedly different in Grey-
hounds compared with other breeds of dog (Court 1999 ). Nearly 40 years ago it
was recognised that Greyhounds tended to recover relatively slowly from the
effects of thiopentone, an ultra-short acting intravenously administered barbiturate
used for anaesthetic induction and short duration anaesthesia in dogs (Court 1999 ).
It was initially speculated that the relatively low body fat content typical of all
Greyhounds may limit the rate of redistribution of drug from the central compart-
ment to adipose tissue within the peripheral compartment, thereby delaying anaes-
thetic recovery. However, a series of elegant studies demonstrated that the
difference may in large part be the result of slower drug metabolism in Greyhounds
(Sams et al. 1985 ; Robinson et al. 1986 ; Sams and Muir 1988 ).
A pharmacokinetic study of thiopentone and thiamylal (a structurally related
thiobarbiturate in clinical use at that time) demonstrated that plasma elimination of
both drugs following intravenous administration was much slower in Greyhounds
(n¼12) compared with mixed-breed dogs (n¼10) (Sams et al. 1985 ). Although it
was possible to calculate pharmacokinetic parameters for both drugs in the mixed
breed dogs, it was not possible to do so for the Greyhounds because plasma
concentrations decreased not only more slowly but also in a non-exponential (i.e.
non-first-order process) manner from 20 to 480 min after drug administration. Over
this same period, drug concentrations in plasma also averaged over 3-fold higher in
Greyhounds compared with non-Greyhound breeds for both drugs. Complete
anaesthesia recovery (time to standing) was also much slower, by more than
3-fold, in Greyhounds. However, in contrast to the thiobarbiturates, for the ultra-
short acting oxybarbiturate, methohexitone, there was a much smaller difference,
with plasma clearance being about 45% lower in Greyhounds, while pentobarbitone
(a medium acting oxybarbiturate) possessed essentially identical pharmacokinetic
parameters for both Greyhound and non-Greyhound breeds. Anaesthesia recovery
times were also somewhat slower with methohexitone but indistinguishable for
pentobarbitone for Greyhounds compared with mixed breed dogs. The pharmaco-
dynamic sensitivity of Greyhounds to thiobarbiturates is not likely to account for
these differences in recovery times, as plasma drug concentrations at recovery were
not lower in Greyhounds compared with mixed-breed dogs. These differences in
anaesthesia recovery times between Greyhound and mixed breed dogs were con-
firmed in another study by the same group that also evaluated possible differences
in cardiovascular and pulmonary effects (Robinson et al. 1986 ). Finally, in a third
study, thiopentone pharmacokinetics was determined before and after treatment of
Greyhounds for 14 days with the liver enzyme inducer, phenobarbitone, and the
results compared with a matched control group of Greyhounds. Significant reduc-
tions in thiopentone concentrations were observed in the phenobarbitone treated
Comparative and Veterinary Pharmacogenomics 55