Comparative and Veterinary Pharmacology

that had previously experienced an adverse reaction to procaine penicillin, com-
pared with a matched control group of horses (Fig. 4 ; Olse ́n et al. 2007 ). However,
the involvement of procaine in these reactions is not certain as the reactions in most
horses occurred within minutes of administration, which is too rapid for absorption
of procaine from intramuscular sites. In addition, the difference in median esterase
activities between reactor and control horses while statistically significant, was
relatively small (less than 10% difference) and this may be of limited biological
significance. The authors also reported a difference in breed susceptibility with
Warmbloods and Thoroughbreds being over-represented out of the 59 identified
reactor horses, although this could simply reflect the population of horses being
treated with procaine penicillin (Fig. 4 ).
The ability of rabbit serum to hydrolyse procaine, as well as the anticholinergic
drug atropine, varies greatly both between and within rabbit strains (Harrison et al.
2006 ). New Zealand white (NZW) rabbits were shown to have a bimodal distribu-
tion of esterase activities (Stampfli and Quon 1995 ) with 70% EM and 30% PM
phenotypes. There was also high concordance between atropine and procaine
esterase activities suggesting that they were metabolised by the same enzyme in
rabbits. However, the molecular genetic basis for this variability is not understood.
Paraoxonase is an arylesterase that hydrolyses and inactivates neurotoxic organ-
ophosphate metabolites (Richter et al. 2009 ). Rabbits have high paraoxonase
activity compared with other species and have been used as a model for studies
of organophosphate (insecticide and nerve gas) toxicity. This enzyme is also
polymorphic in both people and rabbits and amino acid variants have been identi-
fied that explain low paraoxonase activity in humans (hPON1Q192R) and rabbits
(rPON1P82S, K93E and S1O1G) (Watson et al. 2001 ).

WarmbloodRiding-

Horse

4

5

6

7

8

9

10

11

Control horses

PABA (

mg/mL)

Breed group composition (%)

0

10

20

30

40

60

50

70

Horses with adversereaction to penicillin

Horse population in

Sweden

ThourougbredEnglish StandardbredTrotter Pony Draft HorseColdbloodIslandic Horse Reactor horses

Fig. 4Adverse reactions to procaine penicillin and serum procaine esterase activity in Swedish
horses (from (Olse ́n et al. 2007 )). Theleft panelshows the breed distribution of horses (n¼59)
with reported adverse reactions to procaine penicillin administration compared with the distribu-
tion of horses in Sweden. Theright panelis a box and whiskers plot (median, interquartile range)
that shows the difference in serum procaine esterase activities (formation ofpara-aminobenzoic
acid (PABA) from procaine) in blood collected from horses that had adversely reacted to procaine
penicillin (n¼29) compared with a matched group of control horses (n¼17)

58 C.M. Mosher and M.H. Court