Patient variation in veterinary medicine: part I. Influence of altered physiological states.
Abstract: 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.
Publication Date: 2010-06-19 PubMed ID: 20557438DOI: 10.1111/j.1365-2885.2009.01139.xGoogle Scholar: Lookup
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Summary
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The research article discusses the significance of considering various physiological and environmental factors that can influence drug pharmacokinetics (PK) in veterinary medicine. It highlights that relying solely on data from young, healthy, single-breed animals can lead to errors in predicting drug exposure and responses in a wide-ranging population of animals.
Research Subject and Objective
- The study focuses on understanding the patient variation in veterinary medicine, specifically relating to pharmacokinetics (PK) — the movement of drugs within the body. The article delves into the possible influencers of drug exposure characteristics.
- The main aim of this research is to highlight the potential risks of predicting drug properties based solely on studies conducted with small groups of young, healthy animals — and usually of a single breed.
- The researchers stress on the necessity to consider a multitude of factors that can influence PK study outcomes, and hence, the pharmacological response.
Identified Factors Influencing Pharmacokinetics
- The research identifies several easily recognizable factors that can alter drug PK in animals, including breed, gender, age, and body weight.
- It also points out less-obvious factors such as diseases, heritable traits (genetics), and environmental conditions, all of which play crucial roles in the pharmacological response to a drug.
The Role of Stressors in Altered Physiological States
- The manuscript provides an insightful overview of various stressors, including disease, inflammation, pregnancy, and lactation, that can significantly modify the PK of drugs.
- These physiological stressors challenge the body’s homeostasis (balance) and can lead to changes in how the body processes drugs.
Implications of Ignoring Covariates
- The article emphasizes the risk of significant error when predicting the dose-exposure relationship within a population, if appropriate covariates like age, weight, and heritable traits are not taken into account.
- Ignoring these factors could potentially lead to incorrect dosing, unpredictable drug responses, and ineffective treatment outcomes, particularly in a diverse animal population under varied clinical situations.
Conclusion and Future Directions
- This manuscript serves as part one of a series discussing patient variations in veterinary medicine. It successfully outlines the potential influence of altered physiological states on drug PK.
- Part II, as per the abstract, is expected to outline the potential impact of other physiological variables on drug PK in further detail.
Cite This Article
APA
Martinez M, Modric S.
(2010).
Patient variation in veterinary medicine: part I. Influence of altered physiological states.
J Vet Pharmacol Ther, 33(3), 213-226.
https://doi.org/10.1111/j.1365-2885.2009.01139.x Publication
Researcher Affiliations
- Center for Veterinary Medicine, Food and Drug Administration, Rockville, MD 20855, USA. marilyn.martinez@fda.hhs.gov
MeSH Terms
- Animals
- Cats / metabolism
- Cattle / metabolism
- Dogs / metabolism
- Drug Therapy / veterinary
- Female
- Horses / metabolism
- Infections / metabolism
- Infections / veterinary
- Inflammation / metabolism
- Inflammation / veterinary
- Kidney Diseases / metabolism
- Kidney Diseases / veterinary
- Lactation / metabolism
- Liver Diseases / metabolism
- Liver Diseases / veterinary
- Pharmacokinetics
- Pregnancy
- Swine / metabolism
Citations
This article has been cited 9 times.- Draghi S, Pavlovic R, Pellegrini A, Fidani M, Riva F, Brecchia G, Agradi S, Arioli F, Vigo D, Di Cesare F, Curone G. First Investigation of the Physiological Distribution of Legacy and Emerging Perfluoroalkyl Substances in Raw Bovine Milk According to the Component Fraction.. Foods 2023 Jun 22;12(13).
- Ural MN, Uney K. Pharmacokinetic Behavior and Pharmacokinetic/Pharmacodynamic Integration of Danofloxacin Following Single or Co-Administration with Meloxicam in Healthy Lambs and Lambs with Respiratory Infections.. Antibiotics (Basel) 2021 Sep 30;10(10).
- Gray P, Jenner R, Norris J, Page S, Browning G. Antimicrobial prescribing guidelines for poultry.. Aust Vet J 2021 Jun;99(6):181-235.
- Raman S, Srinivasan G, Brookhouser N, Nguyen T, Henson T, Morgan D, Cutts J, Brafman DA. A Defined and Scalable Peptide-Based Platform for the Generation of Human Pluripotent Stem Cell-Derived Astrocytes.. ACS Biomater Sci Eng 2020 Jun 8;6(6):3477-3490.
- Mzyk DA, Bublitz CM, Martinez MN, Davis JL, Baynes RE, Smith GW. Impact of bovine respiratory disease on the pharmacokinetics of danofloxacin and tulathromycin in different ages of calves.. PLoS One 2019;14(6):e0218864.
- Toutain PL, Bousquet-Mélou A, Damborg P, Ferran AA, Mevius D, Pelligand L, Veldman KT, Lees P. En Route towards European Clinical Breakpoints for Veterinary Antimicrobial Susceptibility Testing: A Position Paper Explaining the VetCAST Approach.. Front Microbiol 2017;8:2344.
- Altan F, Uney K, Er A, Cetin G, Dik B, Yazar E, Elmas M. Pharmacokinetics of ceftiofur in healthy and lipopolysaccharide-induced endotoxemic newborn calves treated with single and combined therapy.. J Vet Med Sci 2017 Jul 19;79(7):1245-1252.
- Schneider M, Kuchta A, Dron F, Woehrlé F. Disposition of cimicoxib in plasma and milk of whelping bitches and in their puppies.. BMC Vet Res 2015 Jul 31;11:178.
- Kreuder AJ, Coetzee JF, Wulf LW, Schleining JA, KuKanich B, Layman LL, Plummer PJ. Bioavailability and pharmacokinetics of oral meloxicam in llamas.. BMC Vet Res 2012 Jun 21;8:85.
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