Comparison of the pharmacokinetics of two formulations of hydroxyethyl starch in healthy horses.
Abstract: A lower molecular weight and molar substitution formulation (130/0.4) of hydroxyethyl starch solution has been shown to have a more sustained effect on COP and similar hemodynamic effects as a higher molecular weight and molar substitution formulation (600/0.75) in healthy horses. In humans, these pharmacodynamic characteristics are coupled with more rapid clearance and decreased adverse coagulation effects and accumulation. The objective of this study was to determine and compare the pharmacokinetics of these two formulations in horses. Eight healthy horses were given a 10 mL/kg bolus of each formulation (600/0.75 and 130/0.4) of hydroxyethyl starch solution in a randomized crossover design. Blood was collected, and plasma was harvested for plasma levels over 24 h. Pharmacokinetic parameters for each horse were estimated from a noncompartmental analysis. Treatment with 600/0.75 resulted in a higher initial plasma concentration (C ), systemic half-life (t ), and overall drug exposure (AUC ) in addition to decreased elimination rate (β), volume of distribution (Vd), and clearance (CL), compared to treatment with 130/0.4 (P < 0.001). The pharmacokinetic findings combined with previous pharmacodynamics findings suggest that 130/0.4 can provide similar benefits to 600/0.75 with a lower risk of accumulation in the circulation.
© 2016 John Wiley & Sons Ltd.
Publication Date: 2016-09-21 PubMed ID: 27650135DOI: 10.1111/jvp.12359Google Scholar: Lookup
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- Journal Article
- Randomized Controlled Trial
Summary
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This research aims to compare the pharmacokinetics of two formulations (130/0.4 and 600/0.75) of hydroxyethyl starch solution in horses. It found that the 130/0.4 formulation provided similar benefits to the 600/0.75 formulation but with a lower risk of accumulation in the circulation.
Research Design and Methods
- The study involved eight healthy horses. Both the 130/0.4 and 600/0.75 versions of the hydroxyethyl starch solution were administered to each horse in a randomized crossover design. The horses received a 10 mL/kg bolus of each formulation.
- Following the administration, blood was collected from the horses and the plasma was harvested to measure plasma levels over 24 hours.
- The pharmacokinetic parameters for each horse were calculated from noncompartmental analysis. This analysis type is a system of measuring a drug’s absorption, distribution, metabolism and excretion (pharmacokinetics) without assuming the body or organs to be compartments.
Findings
- The study found that treatment with the 600/0.75 formulation resulted in a higher initial plasma concentration (C), longer systemic half-life (t), and greater overall drug exposure (AUC) compared to the 130/0.4 formulation.
- The 600/0.75 formulation also demonstrated a decreased elimination rate (β), lower volume of distribution (Vd), and slower clearance (CL) in comparison with the 130/0.4 version.
- All these differences in pharmacokinetic parameters were statistically significant with p value less than 0.001.
- Given these findings coupled with previous pharmacodynamics studies that document similar hemodynamic effects of both formulations, the research concludes that the 130/0.4 formulation provides similar therapeutic benefits as the 600/0.75 formulation, but with a lower risk of drug accumulation in the horses’ bloodstream.
Implications
- This study is crucial to veterinary medicine as it provides evidence to guide the selection of hydroxyethyl starch formulation for horses. With the data provided, veterinarians can choose to use the 130/0.4 formulation for similar effects but mitigate potential adverse coagulation effects and drug accumulation, which are common issues with the 600/0.75 formulation.
- These findings also add to the existing body of equine pharmacokinetics research and could further understanding of drug behavior in horses.
Cite This Article
APA
Epstein KL, Bergren A, Nie B, Arnold RD, Brainard BM.
(2016).
Comparison of the pharmacokinetics of two formulations of hydroxyethyl starch in healthy horses.
J Vet Pharmacol Ther, 40(3), 309-313.
https://doi.org/10.1111/jvp.12359 Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
- Department of Clinical Studies, Cummings School of Veterinary Medicine, Tufts University, Grafton, MA, USA.
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.
- Department of Drug Discovery and Development, Harrison School of Pharmacy, Auburn University, Auburn, AL, USA.
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
- Department of Small Animal Medicine and Surgery, College of Veterinary Medicine, University of Georgia, Athens, GA, USA.
MeSH Terms
- Animals
- Blood Coagulation
- Chemistry, Pharmaceutical
- Cross-Over Studies
- Half-Life
- Horses / metabolism
- Humans
- Hydroxyethyl Starch Derivatives / pharmacokinetics
- Molecular Weight
- Plasma Substitutes / pharmacokinetics
Citations
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