Body fluid and endometrial concentrations of ketoconazole in mares after intravenous injection or repeated gavage.

This research article presents findings on the concentrations of the drug ketoconazole in the body fluids and endometrium of horses following oral administration or intravenous injection. It was observed that mean peak concentrations of ketoconazole in serum, synovial fluid, peritoneal fluid, endometrium, and urine were recorded at different time intervals after administration, and the drug’s bioavailability was estimated to be 23 per cent.

Methodology

• The study involved the administration of ketoconazole to seven healthy adult horses. The drug was administered in two ways – orally and via an intravenous injection.
• A healthy mare received a single oral dose of ketoconazole in a 50ml corn syrup preparation at 30 mg/kg bodyweight (bwt). The drug’s presence was then tested in the mare’s serum.
• Six other horses received ketoconazole intragastrically (i.e., directly into the stomach) in 0.2 N HCl. The horses were given five consecutive doses of 30 mg/kg bwt at 12-hour intervals.
• Following administration, ketoconazole concentrations were measured in serum, synovial fluid, peritoneal fluid, cerebrospinal fluid (CSF), urine, and the endometrium.

Results

• Following the single oral administration, no traces of ketoconazole were detected in the mare’s serum.
• After intragastric administration to the other horses, the mean peak serum concentration was found to be 3.76 micrograms/ml at around 1.5 to 2 hours post-administration.
• Mean peak concentration in the synovial fluid, the fluid that reduces friction in the joints, was 0.87 micrograms/ml about 3 hours after the fifth dose. The peritoneal fluid, fluid in the abdominal cavity, showed a similar trend with a mean peak concentration of 1.62 micrograms/ml three hours after the fifth dose.
• The mean peak endometrial concentration was 2.73 micrograms/ml recorded two hours post the fifth dose. Significantly, ketoconazole was found in the cerebrospinal fluid (CSF), which envelops the brain and spinal cord, of only one of the six horses, with a recorded concentration of 0.28 micrograms/ml three hours after the fifth dose.
• The highest measured concentration of ketoconazole was in urine, at 6.15 micrograms/ml, two hours after the final dose.
• A single injection of ketoconazole was also given intravenously to one of the mares, with the drug’s elimination rate estimated at 0.22 per hour. The bioavailability (the degree and rate at which a substance is absorbed into a living system) of the drug after oral administration was calculated to be at 23 per cent.