PHARMACOKINETICS OF SINGLE INTRAVENOUS AND SINGLE AND MULTIPLE-DOSE ORAL-ADMINISTRATION OF RIFAMPIN IN MARES

The disposition of rifampin in six healthy mares after single intraven ous (i.v.) and oral (p.o.) doses and after seven oral doses of 10 mg/k g administered twice a day was investigated using a high performance l iquid chromatographic (HPLC) method. Pharmacokinetic variables for rif ampin determined using the HPLC method were comparable to variables re ported from earlier studies utilizing a microbiological assay. Desasce tylrifampin, a major metabolite of the parent compound, could not be d etected in the serum but was detected at low concentrations in urine. Mean trough concentrations of rifampin increased from the first to the second dose of the multiple dose oral study and then remained unchang ed through 72 h. At 84 h after the first dose (i.e. 12 h after the fin al dose) the rifampin concentration was significantly decreased (P = 0 .001). The harmonic mean of the half-life of rifampin decreased signif icantly from 13.3 h after a single oral dose of 7.99 h after the seven th oral dose. The mean serum protein binding of rifampin over the conc entration range of 2-20 mug/ml was 78%. Mean trough serum concentratio ns of unbound rifampin after multiple oral doses ranged from 0.67 mug/ ml at 24 h to 0.40 mug/ml at 72 h. The mean unbound serum rifampin con centration at 84 h (i.e., 12 h after the final dose) was 0.30 mug/ml. Trough concentrations and the 84-h sample concentration of unbound rif ampin exceeded the minimum inhibitory concentration for most gram posi tive bacterial isolates from horses reported in this study. All organi sms with minimum inhibitory concentrations less than 0. 1 25 mug/ml we re considered susceptible. Based on the pharmacokinetics of rifampin a fter p.o. administration, we concur with the current dosage recommenda tion of 10 mg/kg twice a day by mouth. At this dose, most streptococci , Rhodococcus equi, and coagulase-positive staphylococci would be cons idered susceptible to rifampin.