Chloramphenicol was administered by constant IV infusion to 7 healthy postpartum cows at rates predicted to approach a steady-state plasma concentration of 5 micrograms/ml. After 8 hours of constant IV infusion, uterine tissues were removed surgically and were assayed for chloramphenicol concentrations. Mean plasma-to-tissue ratios of chloramphenicol concentrations were 3.05, 3.63 (6 cows only), and 3.22 for caruncles, endometrium, and uterine wall, respectively. Plasma-to-tissue ratios of the 3 tissues were not significantly different (P greater than 0.10). Intrauterine (IU) injections of chloramphenicol (20 mg/kg of body weight) were administered to 3 healthy postpartum cows. The mean value of the fraction of the drugabsorbed from the uteri of these cows was 0.04. Mean concentrations of chloramphenicol were 43.8 micrograms/g in caruncles, 34.6 micrograms/g in endometrium, 2.8 micrograms/g in uterine wall, and 2.9 micrograms/ml in plasma 8 hours after IU injections. Chloramphenicol has now been banned for use in food-producing animals in the United States because of its potential for causing toxicosis in human beings. It is illegal to use chloramphenicol in food-producing animals in the United States and in some other countries as well. This includes use by the IU route of administration because chloramphenicol and most drugs are absorbed from the uterus into the bloodstream and are distributed to milk and tissues.

The pharmacokinetics and estimated bioavailability of amoxicillin were determined after IV, intragastric, and IM administration to healthy mares. After IV administration of sodium amoxicillin (10 mg/kg of body weight), the disposition of the drug was best described by a 2-compartment open model. A rapid distribution phase was followed by a rapid elimination phase, with a mean +/- SD half-life of 39.4 +/- 3.57 minutes. The mean volume of distribution was 325 +/- 68.2 ml/kg, and the mean body clearance was 5.68 +/- 0.80 ml/min.kg. It was concluded that frequent IV administration of sodium amoxicillin would be required to maintain therapeutic plasma concentrations of amoxicillin, and thus, the use of this dosage form should be limited to the initiation of treatment or to intensive care situations. After intragastric administration of amoxicillin trihydrate (20 mg/kg), 5% cherry-flavored suspension, the drug was rapidly, but incompletely, absorbed and rapidly eliminated (mean half-life of the decline phase of the plasma amoxicillin concentration-time curve, 51 minutes). The mean estimated bioavailability (fractional absorption) of the administered dose was 10.4%, and the mean peak plasma amoxicillin concentration was 2.73 microgram/ml at 1.5 hours after dosing. In one horse with clinical signs of abdominal discomfort and diarrhea, the absorption of amoxicillin from the gastrointestinal tract was delayed and the fraction absorbed was increased. It was concluded that this oral dosage form could be recommended only for the treatment of infections caused by bacteria that are highly susceptible to amoxicillin, that frequent dosing would be necessary, and that absorption may be inconsistent in horses with gastrointestinal disease. In 2 subsequent phases, amoxicillin trihydrate (10 mg/kg) was administered IM as either a 10% (100 mg/ml) or a 25% (250 mg/ml) aqueous suspension. For both formulations, plasma amoxicillin concentration peaked 45 minutes after dosing (2.08 microgram/ml for the 10% suspension and 0.98 microgram/ml for the 25% suspension). Thereafter, mean amoxicillin concentrations > 0.5 microgram/ml persisted for 24 hours, and the values achieved with the 10% suspension were approximately twice as high as those achieved with the 25% suspension throughout the sample collection period. It was estimated that absorption was complete (100%) within 24 hours after IM administration of the dose as 10% aqueous suspension, but was incomplete by 24 hours after administering the same dose as a 25% suspension. This suggests that a large portion of the latter dose remained as a precipitate at the injection site. It was concluded that amoxicillin trihydrate should be administered IM to horses as a 10%, rather than a 25%, suspension. A dosage of 10 mg/kg administered at 12-hour intervals should maintain plasma concentrations > 1 microgram/ml and should be effective in treating infections caused by bacteria that are inhibited by low concentrations of amoxicillin. This dosage regimen does not constitute broad-spectrum treatment and may be limited by the relatively large injection volume and the discomfort associated with administration.

The tarsocrural joints of 11 horses were inoculated with 1.2 to 2.16 x 10(6) viable Staphylococcus aureus organisms susceptible to a trimethoprim-sulfadiazine (TMP-SDZ) combination with minimal inhibitory concentration (MIC) of 0.25 microgram of TMP/ml and 4.75 microgram of SDZ/ml. Antimicrobial treatment consisted of oral administration of a TMP-SDZ combination-30 mg/kg of body weight given once daily (group-1 horses) or 60 mg/kg given as 30 mg/kg every 12 hours (group-2 horses). Paired serum and synovial fluid samples were obtained before intra-articular inoculation with the S aureus, after inoculation with S aureus but before antimicrobial treatment, and after inoculation at various hourly intervals after oral administration of the TMP-SDZ combination. The TMP-SDZ combination was administered daily in the 2 dosages for 21 days. Samples were collected after day 3 of repetitive drug administration so that drug steady-state concentration would have been achieved. Serum and synovial fluid samples were analyzed for TMP and SDZ concentrations. Administration of the TMP-SDZ combination at a dosage of 30 mg/kg once daily was not effective in maintaining TMP or SDZ concentrations above the MIC of TMP-SDZ for the S aureus (0.25 and 4.75 microgram/ml for TMP and SDZ, respectively) in the infected synovial fluid or in maintaining adequate TMP concentration in the serum. The alternative use of the TMP-SDZ combination at a dosage of 60 mg/kg given as 30 mg/kg every 12 hours was effective in maintaining serum and synovial fluid concentrations of TMP and SDZ that were greater than the MIC for the infective organism. Sulfadiazine concentration was significantly (P less than or equal to 0.05) lower in the infected synovial fluid sample than that in the corresponding serum sample. We concluded that administration of 60 mg of TMP-SDZ/kg given as 30 mg/kg every 12 hours is more effective than 30 mg/kg given once daily for the treatment of equine infectious arthritis caused by organisms for which the MIC of TMP-SDZ is less than or equal to 0.25-4.75 microgram/ml.

Tissue drug residue research often involves the killing of an animal every time tissue concentrations are determined. To decrease the number of animals required to perform tissue depletion studies and to circumvent the statistical problems associated with determining tissue depletion kinetic properties, using multiple animals, the renal depletion profile of gentamicin from individual sheep was studied, using a bilateral renal translocation technique. Seven ewes were surgically altered, allowed to stabilize, and then allocated into 2 groups; groups-1 sheep (n = 4) were given 3 mg of gentamicin/kg, IM, q 12 h for 10 days, and group-2 sheep (n = 3) were not given gentamicin. The kidneys from all ewes were biopsied 9 times over 74 days after the termination of gentamicin treatment. The renal concentrations of gentamicin were measured by use of a validated tissue digestion procedure coupled with a liquid-phase fluorescence polarization immunoassay. On days 75 and 77 after the end of gentamicin treatment, all ewes were euthanatized and necropsied. The concentrations of gentamicin in the biopsy specimens ranged from 71.9 to 183 microgram/g on days 1 and 2 after dosing, and decreased to concentrations ranging from 3.99 to 7.35 microgram/g on days 73 and 74 after the end of dosing. The decrease in renal gentamicin concentrations was best described by a biexponential equation, The early phase half-life was 2.8 days, whereas the terminal phase half-life was 59 days (harmonic means). There was no difference in the appearance or histologic features of the kidneys from groups 1 and 2. The only lesions noticed were linear fibroses that were attributed to the biopsy procedure.