PHARMACOKINETIC MODELING IN AQUATIC ANIMALS .1. MODELS AND CONCEPTS

While clinical and toxicological applications of pharmacokinetics have continued to evolve both conceptually and experimentally, pharmacokinetic modeling in aquatic animals has not progressed accordingly. In this paper we present methods and concepts of pharmacokinetic modeling in aquatic animals using multicompartmental, clearance-based, non-compartmental and physiologically-based pharmacokinetic models. These models should be considered as alternatives to traditional approaches, which assume that the animal acts as a single homogeneous compartment based on apparent monoexponential elimination. Multicompartmental models are a necessary increase in complexity when elimination is biphasic or when there is a widely different distribution between high perfusion and low perfusion tissues. Alternatives to traditional rate-constant based models are clearance-based compartmental models, which have parameters that may be interpreted in terms of the controlling physiological and biochemical processes. Non-compartmental methods characterize uptake, distribution, elimination, and persistence without making assumptions about the underlying model topology. Development of physiologically-based models is highly desirable because they allow extrapolation to other species, body sizes and environmental conditions. © 1990.