Comparison of the pharmacokinetics of two formulations of hydroxyethyl starch in healthy horses.

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.