Species differences in pharmacokinetics and pharmacodynamics

Area of Science:

• Veterinary Pharmacology
• Comparative Physiology
• Animal Health

Background:

• Veterinary medicine treats diverse species with unique genetic traits and physiological differences.
• Determining rational drug dosing regimens is a significant challenge due to inter- and intra-species variations.
• Drug response variability stems from differences in pharmacokinetics (PK) and pharmacodynamics (PD).

Purpose of the Study:

• To highlight key species differences in drug PK and PD within domestic animals.
• To explore the physiological, patho-physiological, and behavioral mechanisms underlying these differences.
• To emphasize the need for species-specific drug evaluation.

Main Methods:

• Review of selected aspects of PK and PD across domestic animal species.
• Analysis of physiological, patho-physiological, and behavioral determinants of drug response.
• Consideration of drug administration modalities and management options.

Main Results:

• Significant interspecies differences in drug absorption, distribution, metabolism, and elimination (ADME) were observed, particularly related to digestive functions.
• Interspecies variations in drug action (PD) are generally less pronounced, except in specialized functions like reproduction.
• Drug metabolism is a major contributor to PK and PD variability, including the formation of active metabolites.

Conclusions:

• Species differences in drug handling and response are numerous, often unpredictable, and preclude broad generalizations.
• Allometric approaches offer some predictive value for interspecies drug extrapolation.
• Each drug requires individual evaluation for each species to ensure efficacy, safety, animal well-being, and protection of the food chain and environment.