Comparative and Veterinary Pharmacology

(Elliott) #1

typical in carnivores. In horses, the variability between animals may be very large
(from pH 5 to 9) and urinary pH displays a bimodal distribution in horse popula-
tions (Houston et al. 1985 ).
Urinary pH may be relevant to overall drug elimination via renal clearance and is
a critical consideration for the actual presence of a drug or its metabolites in urine.
This is a direct and major interest for doping control as well as for the treatment of
some lower urinary tract infections. Salicylic acid (SA) is extensively conjugated to
glucuronic acid in herbivorous species, forming a hydrophilic glucuronoconjugate
with a low pKa (approximately 2.5) and a high renal clearance. In the alkaline urine
of herbivores, the SA conjugate is wholly in the ionised form and therefore cannot
be re-absorbed by the nephron. This leads to the rapid elimination of SA or of any
derived glucuronide in herbivores. Urinary pH may also be relevant for drugs with a
low renal clearance, as in the case of phenylbutazone (PBZ) in the horse. In horses,
renal PBZ clearance is less than 10% of total clearance (Authie ́et al. 2009 ) but the
actual urinary level of PBZ in post-race urine is strongly correlated with the pH,
with higher concentrations found in alkaline urine than in more acidic urine
(Houston et al. 1985 ). See chapter, “Veterinary Medicines and Competition Ani-
mals” of this text for further discussion.


11 Specificity in Drug Administration and

Disposition in Poultry

Variability amongst bird species is as large as that observed between mammals and
each species must be treated as a species in its own right. Marked variability has
been noted for the disposition of three NSAIDs (sodium salicylate (SA), meloxicam
and flunixin) in 5 bird species (ostrich, pigeon, duck, turkey, and chicken).
Ostriches had the fastest elimination rate for all 3 NSAIDs. In chickens, flunixin
had a half-life (5.5 h) that was 10 times longer than the other bird species (0.17–
0.6 h). On the other hand, for SA the hierarchy was different with a shorter half-life
in the chicken (3.13 h) than in pigeon (14.93 h) and duck (5.41 h). Therefore, no
general principles allow extrapolation from one avian species to another and the
rational design of dosage schedules must be based on data generated separately
in each.
Another consideration in poultry medication is that drugs are most often admi-
nistered collectively at the flock level and by the oral route (90% of all treatments).
To achieve an effective collective treatment in poultry, special attention must be
paid to poultry feeding and drinking behaviours and to the species characteristics of
digestive tract physiology. For a comprehensive review on drug administration to
poultry, see Vermeulen et al. ( 2002 ).
Drinking water is the preferred mode of administration for drugs, especially for
antibiotics, because diseased birds usually tend to stop eating but will usually
continue to drink. To achieve an effective dose the drug concentration in the


Species Differences in Pharmacokinetics and Pharmacodynamics 41

Free download pdf