Consideration of sheep as a minor species: comparison of drug metabolism and disposition with other domestic ruminants.

The processes which determine bioequivalence of a given drug among species are many, and include absorption from a site of administration, renal, biliary and intestinal elimination, sequestration (in particular, binding to proteins or other macromolecules), distribution and redistribution, biotransformation, and receptor population density and uniqueness. The present review is limited to physiologic and pharmacologic parameters which affect drug distribution, elimination, and metabolism, primarily because these are areas where sufficient data is available to make comparisons between sheep and other ruminants. The literature suggest a high degree of similarity among domestic ruminants in the distribution and elimination of drugs that are not metabolized but eliminated by passive processes such as renal glomerular filtration. Although the data are not as uniform as when conducted under rigorous control in the same laboratory setting, it is possible to predict very similar pharmacokinetic profiles for many of the antimicrobials between cattle, sheep and goats. Metabolic scaling of kinetic parameters could be predicted in comparative studies conducted under well-controlled conditions, in which case the greatest similarities would occur among the small ruminants with values being somewhat dissimilar between sheep or goats and cattle. Plasma protein binding of drugs appears to be very similar among the ruminants, and its influence on drug distribution and elimination does not appear to vary appreciably between cattle and sheep. There is, however, very little definitive data which describes binding parameters, and there is very little data of any kind on binding to caprine albumin other plasma proteins of the goat. Sheep apparently differ from cattle, however, in transcortin concentrations, and this could affect the distribution and elimination of prednisolone or any other synthetic steroid which exhibits high affinity binding to this transport protein. Among the drug substances for which comparative information is available, there is very little to suggest qualitative differences in routes of metabolism among ruminants. There appears to be a remarkable degree of similarity in both major and minor pathways of drug metabolism among these species, and in fact, no documentable differences of a qualitative nature have been found. It should be noted, however, that documentable differences would only be established in a direct comparison of species conducted in the same laboratory under carefully controlled conditions. Such conditions would necessarily include assurance of no recent exposure to enzyme inducing agents or inhibitors or to agents which could deplete endogenous substances necessary to the enzymatic process.(ABSTRACT TRUNCATED AT 400 WORDS)