Pharmacokinetics of the calcium-channel blocker diltiazem after a single intravenous dose in horses.

This research investigates how the drug diltiazem, commonly used in human and veterinary medicine as a calcium-channel blocker, is distributed and metabolized in horses after a single intravenous injection. Results show that diltiazem is rapidly distributed and eliminated in horses, with a quicker terminal half-life than in humans or dogs.

Methodology

• The experiment was conducted on eight healthy horses.
• Each horse received an intravenous dose of diltiazem HCl at a dose rate of 1mg/kg over a period of 5 minutes.
• Blood samples were drawn at regular intervals following drug administration.

Results Collection

• The plasma concentrations of diltiazem and desacetyldiltiazem (a metabolite of diltiazem) were measured using high-performance liquid chromatography.
• A second unidentified metabolite was also detected, however, it was not identified because of a lack of a standard sample for comparison.
• Data analysis was done using nonlinear least-squares regression analysis.

Findings

• The median peak plasma concentration of diltiazem was 727 ng/mL.
• The plasma diltiazem concentration vs. time data were best described by a two-compartment model with first-order drug elimination.
• The distribution half-life was 12 minutes, the terminal half-life was 93 minutes, and the mean residence time was 125 minutes.
• The total plasma clearance rate was calculated to be 14.4 mL/kg/min, and the volume of distribution at steady-state was determined to be 1.84 L/kg.
• The normalized ratio of the area under the curve (AUC) of desacetyldiltiazem to the AUC of diltiazem was found to be 0.088.

Conclusions

• The researchers concluded that diltiazem is quickly distributed and eliminated in horses, suggesting a shorter terminal half-life than what is reported in humans and dogs.
• Due to the reported low pharmacologic activity of the diltiazem metabolites in the plasma, the researchers determined these concentrations are not clinically important.