Computational Comparative Pharmacology: Designing Better Drugs for Animals (and Humans)

A lack of species-specific pharmacokinetic data is a major clinical challenge for veterinarians. Without these data, it becomes difficult to select optimal dosage regimens that maximize the probability of positive therapeutic outcomes and minimize potential safety concerns. Often, a veterinary dosage regimen must be extrapolated from other species (or humans). In addition to the added risk to the animal of suboptimal dosing, there is also a concern of tissue residues in animals being raised for food (eg, meat and milk). Therefore, tissue residues are a unique concern in veterinary medicine because indirect exposure to drugs and their metabolites through eating meat or milk could potentially negatively impact human health.
In this webinar, we looked at the physiological differences between and within major domestic animal species (cow, horse, dog, cat), how these can alter the pharmacokinetics of drugs, and how these effects vary depending on the physicochemical properties of the drug. Physiologically-based pharmacokinetic (PBPK) modeling is a computational pharmacology technique for predicting the absorption, distribution, metabolism, and excretion of drugs in humans and other animal species. We showed how even a minimal PBPK model can be a useful tool to predict how inter-species differences in body composition and excretory organ (ie, kidney and liver) function can alter plasma and tissue drug concentrations.
Modeling and simulation can help veterinarians provide better care for animals and guide research study design thereby maximizing the knowledge gained from research studies whilst minimizing the number of animals used.