Comparative and Veterinary Pharmacology

expression also accounts for decreased clearance of thiobarbiturates or other drugs
in Greyhounds.

2.1.6 Esterases in Horses and Rabbits

Benzylpenicillin is the most frequently used penicillin in equine therapy, and is
often given intramuscularly as a procaine salt. However, occasionally horses
demonstrate adverse effects following injection of procaine penicillin ranging
from sweating, staggering and tachycardia to seizures and death (Olse ́n et al.
2007 ). While this has been attributed primarily to an immune-mediated hypersen-
sitivity reaction to the penicillin, procaine also has the potential to cause cardiotoxic
and neurotoxic effects (including seizures) as the result of inhibition of voltage-
gated sodium channels. Procaine is normally rapidly metabolised by plasma esterase
to the nontoxic metabolitespara-aminobenzoic acid (PABA) and diethylaminoetha-
nol following intramuscular injection and is unlikely to reach toxic concentrations
(Tobin et al. 1976 ). However, in a study of plasma collected from 27 horses
including Thoroughbreds and Standardbreds, high variability in plasma procaine
esterase activities was observed between individual horses, although the distribution
of activities was considered to be uniform (i.e. not bimodal with clear PM and EM
phenotypes) (Tobin et al. 1976 ). The possible molecular genetic basis for this
variability in esterase activities in horses has not been explored. A recent Swedish
study demonstrated that plasma procaine esterase activities were lower in horses

Propofol hydroxylation

0

2

4

6

8

10

Mixed Beagle Greyhound

Dog Breed

nmoles / min / mg protein

0

0.1

1.0

Greyhounds

Mixed – breed dogs

Propofol conc (

μg / ml )

10.0

10 20 30

Time (min)

40 50 60

Fig. 3Propofol clearance from plasma in vivo and propofol hydroxylation by liver in vitro is
slower in Greyhounds compared with mixed-breed and Beagle dogs. Theleft panel(from Zoran
et al. ( 1993 )) shows differences in mean propofol concentrations between Greyhound (n¼10) and
mixed breed (n¼8) dogs after intravenous administration of 5 mg/kg body weight. Thearrows
indicate time of return of the righting reflex (filled arrow) and ability to stand (open arrow). The
right panel(adapted from Court et al. ( 1999 )) shows differences in propofol hydroxylation activity
measured by HPLC of in vitro incubations using liver microsomes prepared from male Grey-
hounds, beagles, and mixed-breed dogs (n¼5 each). The points represent data from individual
dog livers, while thehorizontal linesindicate the mean values of each group

Comparative and Veterinary Pharmacogenomics 57