The pharmacokinetics and bioavailability of rifampin were determined after IV (10 mg/kg of body weight) and intragastric (20 mg/kg of body weight) administration to 6 healthy, adult horses. After IV administration, the disposition kinetics of rifampin were best described by a 2-compartment open model. A rapid distribution phase was followed by a slower elimination phase, with a half-life (t1/2[beta]) of 7.27 +/- 1.1 hours. The mean body clearance was 1.49 +/- 0.41 ml/min.kg, and the mean volume of distribution was 932 +/- 292 ml/kg indicating that rifampin was widely distributed in the body. After intragastric administration of rifampin in aqueous suspension, a brief lag period (0.31 +/- 0.09 hour) was followed by rapid, but incomplete, absorption (t1/2[a] = 0.51 +/- 0.32 hour) and slow elimination (t1/2[d] = 11.50 +/- 1.55 hours). The mean bioavailability (fractional absorption) of the administered dose during the first 24 hours was 53.94 +/- 18.90%, and we estimated that 70.0 +/- 23.6% of the drug would eventually be absorbed. The mean peak plasma rifampin concentration was 13.25 +/- 2.70 microgram/ml at 2.5 +/- 1.6 hours after dosing. All 6 horses had plasma rifampin concentrations > 2 microgram/ml by 45 minutes after dosing; concentrations > 3 microgram/ml persisted for at least 24 hours. Mean plasma rifampin concentrations at 12 and 24 hours after dosing were 6.86 +/- 1.69 microgram/ml and 3.83 +/- 0.87 microgram/ml, respectively. We tested 162 isolates of 16 bacterial species cultured from clinically ill horses for susceptibility to rifampin. All strains of coagulase-positive staphylococci, Streptococcus zooepidemicus, Str equi, Str equisimilis, Rhodococcus equi and Corynebacterium pseudotuberculosis were highly susceptible to rifampin (minimal inhibitory concentration [MIC] less than or equal to 0.25 microgram/ml).

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.

The efficacy of febantel paste formulation (6 and 12 mg/kg) against natural infections of gastrointestinal helminths in lambs (n = 33) in Kentucky was evaluated in a controlled test. For the test, 23 lambs were treated orally (17 at 6 mg/kg and 6 at 12 mg/kg) and 10 lambs were not treated. Removals at both dosages in treated lambs were 95% to 100% for species of immature and mature Haemonchus, Trichostrongylus, and Cooperia; and mature Ostertagia females, Nematodirus, and Strongyloides. For immature Nematodirus, removals were 92% and 77% at the dosages of 6 and 12 mg/kg, respectively. Only a few specimens (av less than 100) of some other species or stages were found in the nontreated group and removal of them (at both dosages) were 94% to 100% for Ostertagia (immature and males), Strongyloides (immature), Oesophagostomum (immature), and Monieiza (mature); and 61% (at 6 mg/kg) and 100% (at 12 mg/kg) for Capillaria (mature), 0% for Trichuris (mature, at both dosages), and 67% (at 6 mg/kg) and 100% (at 12 mg/kg) for Oesophagostomum (mature).

Anthelmintic efficacies of fenbendazole, ivermectin, and levamisole were evaluated against naturally acquired infections of Nematodirus battus in lambs. Four groups of 10 lambs each were used. Oral administration of 8 mg of levamisole/kg of body weight or 5 mg of fenbendazole/kg significantly (P < 0.01) reduced the degree of infection by N battus (adults) by > 99%. An oral formulation of 200 microgram of ivermectin/kg was 98% effective (P < 0.01). Numbers of other Nematodirus spp (including N filicolis and N spathiger) were significantly reduced.

In vitro twitch characteristics of the semimembranosus muscle were evaluated in 9 clinically normal horses, in 15 horses with chronic intermittent rhabdomyolysis (CIR) and in 2 horses with myotonia. Effects of phenytoin on in vitro muscle twitch and clinical signs of CIR and myotonia were evaluated in these same horses. Times to 90% relaxation were prolonged in the horses with CIR (mean +/- SEM, 186 +/- 5.9 ms) and in 2 horses with myotonia (197 and 177 ms) compared with those in clinically normal horses (mean +/- SEM, 146 +/- 2.1 ms). Horses with CIR also had significantly (P < 0.05) longer times to 50% relaxation, compared with clinically normal horses. In the group of horses with CIR, Standardbreds had significantly (P < 0.05) longer times to 90% and 50% relaxation, compared with Thoroughbreds. Times to 100% peak tension did not differ among the groups. Administration of phenytoin directly into a muscle preparation bath solution had no effect on muscle twitch properties. After the initial muscle biopsy, phenytoin was administered orally for 7 to 10 days to 4 horses with CIR, 2 myotonic horses, and 2 clinically normal horses before repeat biopsy from the same site in the contralateral semimembranosus muscle. Times to 90% relaxation decreased from 197 and 177 ms to 144 and 126 ms, respectively, in the 2 myotonic horses, from a mean of 192 (+/- 9) ms to 170 (+/- 9) ms in the 4 horses with CIR and remained unchanged (154 and 140 ms before vs 155 and 139 ms after treatment) in the 2 clinically normal horses. Phenytoin treatment of 8 horses with CIR was associated with excellent clinical response in 7; 1 horse became lame, which prevented evaluation of the drug, and the other horse with normal muscle twitch properties continued to have seasonally severe CIR. Of the 9 horses with CIR that were not treated, 4 were lost to evaluation, 3 continued to be affected (but 1 of these often performed well), and 3 were reported to perform satisfactorily. After 10 days of treatment, the 2 myotonic horses had no change in gait or myotonic dimpling and myotonic discharges persisted, although subjectively, they were slightly decreased. Phenytoin appears to be useful clinically for treating horses with CIR.

Primigravid swine were vaccinated orally with a live enterotoxigenic Escherichia coli (ETEC) strain that produces pilus antigen K99. The titers of K99 antibody in colostrum and milk of vaccinates remained higher than those of nonvaccinated controls through the first lactation after vaccination (4 weeks). Some control swine had low titers of K99 antibody in colostrum or developed low titers of K99 antibody in milk during lactation. Lacteal K99 antibody titers of vaccinates dropped to control levels during the second lactation, 6 months after vaccination. Pigs suckling vaccinates and controls were equally susceptible to challenge exposure to K99+ ETEC during the second lactation. Orally vaccinated swine given a parenteral booster vaccination (with killed K99+ ETEC) during their second gestation had K99 antibody in milk through their second lactation. During the second lactation, these orally vaccinated parenterally revaccinated swine had higher titers of K99 antibody in postcolostral milk than did nonvaccinated controls, controls given only the parenteral booster injection, or controls vaccinated parenterally during both gestations.

The influence of immunosuppression by T-2 mycotoxin on the fungal disease aspergillosis was investigated in rabbits. Four groups of rabbits (groups 1A, 1B, 3A, and 3B) were given 0.5 mg of T-2 toxin/kg of body weight/day, PO; in addition, rabbits of groups 3A and 3B were exposed to aerosols of Aspergillus fumigatus conidia from days 7 through 16. Rabbits of groups 2A and 2B were exposed to A fumigatus aerosols, but were not given T-2 toxin, and rabbits of group 0 served as controls. Two rabbits of group 1A, 1 rabbit of group 1B, and 1 rabbit of group 3A died before scheduled necropsy. Rabbits of groups 1A, 2A and 3A were killed and necropsied on day 17, and the remaining rabbits (groups 0, 1B, 2B, and 3B) were killed and necropsied on day 28. Changes caused by T-2 toxin included leukopenia, marginal anemia, and increased number of and morphologic changes in nucleated erythrocytes by day 21, followed by a regenerative hematologic response. Serum alkaline phosphatase and sorbitol dehydrogenase activities and antibody response to A fumigatus (as measuredby an indirect hemagglutination test) were decreased by T-2 toxin ingestion. Rabbits with aspergillosis had leukocytosis, increased PCV, and increased antibody response to A fumigatus. Histologic lesions consisting of centrilobular hepatocellular swelling, portal and periportal fibrosis, and lymphocyte necrosis and/or depletion within secondary lymphoid tissue were observed in most rabbits treated with T-2 toxin. Normal defense mechanisms against A fumigatus infection were compromised by T-2 treatment, as evidenced by the severity and extent of lung lesions, greater number of hyphal elements observed, and greater number of colonies of A fumigatus isolated from rabbits of groups 3A and 3B. There were no significant changes in group-0 rabbits.

Twenty-four male domestic shorthair cats were used to evaluate the acute and chronic effects of a single, toxic but sublethal, orally administered dose of chlorpyrifos. A dose of 10 mg/kg of body weight did not induce clinical signs of toxicosis, but a dosage of 40 mg/kg induced clinical signs of toxicosis, and 1 of 12 cats died. Chlorpyrifos given at a dosage of 0.1 mg/kg to 2 cats reduced whole blood and plasma cholinesterase (Che) activities to values obtained after cats were given doses that induced clinical signs of toxicosis. Regeneration time for whole blood and plasma Che activities ranged from 7 to 28 days. Brain Che activity was considerably decreased in 1 cat that died 4.5 hours after dosing, but was normal in all others at 28 days after dosing. Other than decreased Che activity, significant changes were not seen in hematologic or serum biochemical values. Toxin-related lesions were not seen during macroscopic or microscopic examination.