Rational dosing of antimicrobial drugs: animals versus humans

The rational dosing of antimicrobial drugs depends on knowledge of physiology, anatomy and pathology, including disease condition, and in major respects these differ between animals and humans and between species of animal. These differences lead to species variation in drug pharmacokinetics, which can be profound. This review highlights selected aspects of species differences in pharmacokinetics and considers underlying mechanisms by reference to ruminant and non-ruminant mammals, birds, fish and bees. For all species it is desirable and should be possible to design dosage schedules based on knowledge of drug pharmacokinetics and pharmacodynamics. There have been many attempts to integrate pharmacokinetic and pharmacodynamic data to provide dosage schedules which optimize efficacy and minimize opportunities for the development of antimicrobial resistance in both laboratory animal studies and human clinical trials. However, there have been relatively few studies in animal species of major veterinary interest. This review summarizes recent studies in four ruminant species (calf, sheep, goat and camel) which have used PK-PD integration to determine for the fluoroquinolone, danofloxacin, AUC/MIC ratios producing (a) bacteriostasis (b) bactericidal activity and (c) elimination of bacteria. Future possible developments in dosage schedule design are considered.