is a metabolic adaptation observed in wild migrating birds and fish (e.g. cod), in
which hepatic steatosis occurs naturally as a consequence of energy storage before
migration. The process of hepatic steatosis is facilitated in these oviparous species,
because the liver is the major site ofde novolipogenesis, which is not the case in
mammals. Foie gras represents a quasi-pure form of acquired and reversible hepatic
steatosis of nutritional origin. The tissue is not diseased, as degenerative events
such as necrosis or cirrhosis never occur, so that the metabolism of drugs is
minimally affected in fattened duck and goose.
Glomerular filtration is not constant in birds, for example in the face of varying
perfusion pressure, and this can have an impact on drug PK. Avian species appear to
be more susceptible to renal ischaemia and tissue damage caused by NSAIDs than
to the gastro-intestinal tract side-effects. Recently, a decline in the vulture popula-
tion in India and Pakistan was observed (Oaks et al. 2004 ) and a direct correlation
was shown between renal residues of diclofenac (a NSAID) and renal failure,
because in these countries the primary food source for vultures is dead domestic
livestock and it was hypothesised that the most probable source of diclofenac
exposure was the consumption by vultures of treated livestock.
12 Species Variability in Drug Administration and
Disposition in Fish
The main farmed fish in Europe are salmon and rainbow trout. Establishing dosing
schedules for drugs in fish must take into account the major differences in anatomy
from mammalian species as well as the husbandry circumstances. Several routes of
administration are possible. The commonest method and the only one practicable
for treating farmed fish (e.g. salmon and trout) is in medicated feed as for anti-
parasitic drugs like praziquantel for removal of tapeworms. This requires sponta-
neous ingestion. As appetite in fish is severely depressed in cases of infection,
antibiotherapy should be prophylactic. Gastric emptying in trout and salmon is a
very slow process compared with mammals. Drug absorption occurs in the
stomach and weak bases are generally well-absorbed, by the classical Hender-
son–Hasselbalch mechanism. Following absorption, a drug undergoes a possible
hepatic first-pass effect, due to a liver portal system as in mammals, and the extent
of bioavailability depends on the extent of hepatic catabolism.
Tetracycline has a low bioavailability in fish (<10%), due to binding with
sea-water-borne divalent cations such as Mg2+and Ca2+. It is noteworthy that
non-bioavailable tetracyclines contaminate the environment. For example, it has
been shown that residues of oxytetracycline in marine sediments were very stable
over months. See chapter, “Veterinary Medicines and the Environment” of this text
for further discussion. Generally, drug bioavailability is lower in fish than
in mammals: for example, 55% for enrofloxacin but only 2% for sarofloxacin
(Martinsen and Horsberg 1995 ).
Species Differences in Pharmacokinetics and Pharmacodynamics 43