Study of intragastric administration of doxycycline: pharmacokinetics including body fluid, endometrial and minimum inhibitory concentrations

The objectives of this study were to determine the pharmacokinetics and tis sue concentrations of doxycycline after repeated intragastric administratio n, and to determine the minimum inhibitory concentrations (MIC) for equine pathogenic bacteria. In experiment 1, 2 mares received a single intragastri c dose of doxycycline hyclate (3 mg/kg bwt), Mean peak serum concentration was 0.22 mu g/ml Ih postadministration. In experiment 2, 5 doses of doxycyc line hyclate (10 mg/kg bwt), dissolved in water, were administered to each of 6 mares via nasogastric tube at 12 h intervals. The mean +/- s.e, peak s erum doxycycline concentration was 0.32 +/- 0.16 mu g/ml 1 h after the firs t dose and 0.42 +/- 0.05 mu g/ml 2 h after the fifth dose. The mean trough serum concentrations were greater than or equal to 0.16 mu g/ml, Highest me an synovial concentration was 0.46 +/- 0.13 mu g/ml and highest mean perito neal concentration was 0.43 +/- 0.07 mu g/ml, both 2 h after the fifth dose . Highest urine concentration was mean +/- s.e, 145 +/- 25.4 mu g/ml 2 h af ter the last dose. Highest endometrial concentration was mean rt s.e. 1.30 +/- 0.36 mu g/ml 3 h after the fifth dose. Doxycycline was not detected in any of the CSF samples, Mean +/- s.e. Vd(area) was 25.3 +/- 5.0 I/kg and me an t(1/2) was 8.7 +/- 1.6 h, In experiment 3, minimum inhibitory concentrat ions of doxycycline were determined for 168 equine bacterial culture specim ens. The MIC90 was less than or equal to 1.0 mu g/ml for Streptococcus zooe pidemicus and 0.25 mu g/ml for Staphylococcus aureus, Based on drug concent rations achieved in the serum, synovial and peritoneal fluids and endometri al tissues and MIC values determined in the present study, doxycycline at a dose of 10 mg/kg bwt per os every 12 h may be appropriate for the treatmen t of infections caused by susceptible (MIC 10.25 mu g/ml) Grampositive orga nisms in horses.