A pharmacokinetic study of digoxin in the horse.

The study analyzes the pharmacokinetics (how a drug is absorbed, distributed, metabolized, and excreted in the body) of the drug digoxin in horses, when administered orally and intravenously. The findings suggest that the oral administration, despite being comparatively less bioavailable, may be safer than intravenous administration due to lower immediate serum digoxin concentrations.

Study Design and Procedure

• The study involved seven healthy adult horses (mares and geldings).
• They were administered digoxin through two separate trials, one orally and the other intravenously.
• The dose for oral administration was 44 micrograms of digoxin per kilogram body weight and 22 micrograms for the intravenous administration.

Results from the Oral Administration Trial

• The oral administration led to a peak serum digoxin concentration of 2.21 ng/ml after approximately 2.29 hours post-administration.
• A second rise in digoxin concentration was observed about 6-8 hours after administration, lasting until around 20 hours after administration.
• The mean bioavailability (the extent and rate at which the drug reaches systemic circulation) was found to be around 23.38%.

Results from the Intravenous Administration Trial

• The pharmacokinetic behaviour of digoxin via intravenous administration was characterized by a two-compartment model, taking into account the distribution and elimination phases.
• The following pharmacokinetic measurements were obtained: distribution rate constant (alpha) was 1.391 per hour, initial serum digoxin concentration determined from the distribution phase (A) was 21.247 ng/ml, elimination rate constant (beta) was 0.0409 per hour, initial serum digoxin concentration determined from the elimination phase (B) was 3.82 ng/ml, and apparent specific volume of distribution uncorrected for protein binding (Vd beta) was 5.003 l/kg.
• The mean beta (the elimination rate constant) corresponded to a biological half-life (time it takes to decrease the drug concentration by half) of 16.9 hours.

Authored Recommendations and Conclusions

• Based on the findings, the authors calculated the theoretically achievable steady-state serum digoxin concentrations for maintenance doses given both orally and intravenously.
• Loading doses (initial higher doses of a drug that may be given at the beginning of a course of treatment before dropping down to a lower maintenance dose) were also calculated for both routes.
• The authors suggest that while the oral administration of digoxin in horses has a lower bioavailability, it might present fewer potential risks due to lower immediate serum concentrations compared to intravenous administration.