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

Abstract

Martinez, M., Modric, S. Patient variation in veterinary medicine: part I. Influence of altered physiological states. J. vet. Pharmacol. Therap.33, 213–226. 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.

Quantitative perfusion analysis of the pancreas and duodenum in healthy dogs by use of contrast-enhanced ultrasonography

“…[43][44][45][46] The variability in perfusion data for the clinically normal dogs in the present study would likely be exceeded in a clinical setting, in which dogs would likely vary much more in cardiovascular characteristics such as cardiac output, vascular tone, hydration, and other factors affecting end-organ perfusion data. The smaller-sized dogs typically had shorter intervals to contrast medium arrival and TPIs than the medium-sized dogs, which could have been caused by differences in blood volume, minute volume, blood pressure, heart rate, or length of microbubble travel from the site of injection to the area of imaging.…”

Bioavailability and pharmacokinetics of oral meloxicam in llamas

“…To determine optimal dosing and treatment intervals necessary to ensure adequate tissue concentrations for clinical efficacy, further studies combining pharmacodynamics with pharmacokinetics and safety trials in llamas are recommended. In addition, various stressors such as disease, inflammation, pregnancy, and lactation have all been shown to affect the pharmacokinetics of medications [28], thus the data reported here may not reflect exact PK parameters in diseased states. Alternative dosing strategies may also be necessary to achieve appropriate levels of therapy for all targeted outcomes (pain relief, fever reduction, decrease in inflammation, or protection against the effects of endotoxin).…”

Pharmacokinetics, pharmacodynamics, toxicology and therapeutics of mavacoxib in the dog: a review

“…Martinez and Modric () have pointed out that ‘when PK data are generated in small groups of normal healthy animals, it is often assumed that these data represent the drug's PK characteristics across the intended patient population'. The statement of Martinez and Modric highlights the importance to extrapolate PK data derived from young healthy animals to older and possibly diseased populations of animals with great caution.…”