Patient variation in veterinary medicine: part I. Influence of altered physiological states

In veterinary medicine, the characterization of a drug's pharmacokinetic (PK) properties is generally based upon data that are derived from studies that employ small groups of young healthy animals, often of a single breed. These are also the data from which population predictions are often generated to forecast drug exposure characteristics in the target population under clinical conditions of use. In veterinary medicine, it is rare to find information on the covariates that can influence drug exposure characteristics. Therefore, it is important to recognize some of the factors that can alter the outcome of PK studies and therefore potentially alter the pharmacological response. Some of these factors are easily identified, such as breed, gender, age, and body weight. Others are less obvious, such as disease, heritable traits, and environmental factors. This manuscript provides an overview of the various stressors (such as disease, inflammation, pregnancy, and lactation) that can substantially alter drug PK. Part II of this series provides an overview of the potential impact of physiological variables such as age, weight, and heritable traits, on drug PK. Ultimately, failure to identify appropriate covariates can lead to substantial error when predicting the dose-exposure relationship within a population.