Biliary elimination and enterohepatic recycling of drugs occur in fish. Topical
treatments are available and fish may be placed in baths for treatment in water. Drug
examples are dichlorvos and trichlorfon, two organophosphates that are used to treat
sea lice infestations. The main challenge of this modality of treatment is the pollution
of the environment and the possible impact on non-target species, as discussed in
chapter, “Veterinary Medicines and the Environment” of this text. The main route
of absorption for drugs directly administered in water is via the gills so that water
properties including pH and composition influence drug absorption, as only unionised
fractions are absorbed. When oxygen tension decreases, the fish passes more water
over its gills for oxygen capture and this can indirectly increase the exposure of the fish
to drugs in solution in the water. A large fraction of drug absorbed by the gills
is initially transported to the kidneys and can undergo a renal first-pass effect.
Moreover, it is noteworthy that enzyme induction at the kidney level in fish exposed
to foreign compounds is observed before corresponding hepatic induction occurs.
The fish kidney is similar to the mammalian kidney but with a renal portal
system; blood from the portal vein bathes the tubules and exposes them to a much
higher fraction of the cardiac output than in mammals. In addition, xenobiotics can
be presented directly to the tubules via the caudal vein. This explains why injections
into muscle should be made (as in poultry and reptiles) in the cranial segment of
the fish.
In fish, drugs may accumulate in fat depots and subsequent removal of feed will
promote mobilisation of lipid reservoirs with redistribution throughout the body.
Drug metabolism is qualitatively similar in fish and mammals for phase I and phase
II processes but the kidney may be the main site of drug metabolism in fish. Fish are
heterotherm animals and water temperature has a major influence on the rate of
drug metabolism, so that the values of PK parameters are variable rather than fixed;
they are temperature-dependent variables. However, acclimatisation is possible and
the same rate of drug metabolism may occur at 5C and 25C, providing the fish are
at their respective acclimatisation temperature. The temperature dependency of
drug PK is an important consideration for drug residues. The elimination half-life
of antimicrobial drugs increases significantly as the temperature decreases, a fall in
temperature from 20 to 10.8C being associated with an increase of up to 100%
in elimination half-life. Ideally, drug dose should be adjusted according to water
temperature, but in clinical practise the dose is normally fixed. Therefore, for
farmed trout and salmon, the withdrawal times, based on temperature dependent
residue levels, are determined indegree days(Cdays). Degree-days are calcu-
lated by multiplying the mean daily water temperatures by the total number of days
measured.. Thus, 160days represents a withdrawal period of 16 days at 10Corof
10 days at 16C. It should be stressed that drug activity can also be temperature
dependent; for example when tested againstAeromonas salmonidae, the MICs for
several quinolones were 2–3-fold higher at 4C than at 15C (Martinsen et al.
1992 ). For an old but still valuable review, see Ingebrigtsen ( 1991 ) and for a more
recent review see Shao ( 2001 ). An exhaustive and searchable data base on drug
residues and PK parameters in aquatic species is available online (Reimschuessel
et al. 2005 ).
44 P.-L. Toutain et al.