Pharmacokinetics of acetazolimide after intravenous and oral administration in horses.

This research study explores the pharmacokinetics, or how the drug moves through the body, of a drug called acetazolamide in horses. It shows that the drug is quickly absorbed, has low bioavailability, and slower elimination when administered orally compared to intravenous (IV) administration.

Study Methods

• The study was conducted on six clinically normal adult horses. These horses were administered with two doses of acetazolamide (one intravenous at 4mg/kg of body weight and one oral at 8mg/kg).
• Blood samples were collected at regular intervals before and after the administration of the drug.
• The acetazolamide concentration in the samples was estimated using high-performance liquid chromatography, a method widely used for detecting and measuring concentrations of organic compounds in a solution.
• The concentration-time data collected from the study was then analyzed.

Study Results

• Following IV administration of acetazolamide, the median mean residence time of the drug in the horses’ bodies was found to be 1.71 +/- 0.90 hours and the clearance rate from the body was 263 +/- 38 ml/kg/h.
• The median steady-state volume of distribution, which indicates the extent of a drug’s distribution in the body after reaching steady-state, was 433 +/- 218 ml/kg.
• When given orally, the average peak of acetazolamide concentration in the horse’s plasma was 1.90 +/- 1.09 microg/ml. The time the drug took to reach this peak concentration was 1.61 +/- 1.24 hours.
• The median oral bioavailability, which is the portion of the drug that enters the circulation when introduced orally and so is able to have an active effect, was found to be 25 +/- 6%.

Study Conclusions

• The oral pharmacokinetic disposition of acetazolamide in horses was found to be characterized by rapid absorption. However, it showed low bioavailability, meaning only a small fraction of the orally administered drug effectively entered the blood circulation.
• The elimination of the drug from the horse’s body was slower for oral administration compared to IV administration.
• The data generated from this study should enable more accurate dosage predictions for using acetazolamide in horses with hyperkalemic periodic paralysis, a genetic disorder that affects the skeletal muscles of horses.