Antiparasitic efficacy of ivermectin against migrating Gasterophilus intestinalis was evaluated in 36 treated and 24 nontreated (n = 12) or vehicle-treated (n = 12) ponies experimentally and naturally infected with G intestinalis and naturally infected with G nasalis. Each pony was experimentally infected with 500 G intestinalis lst instars in 2 divided doses on days -14 and -7 before treatment. On day 0, ivermectin was administered at the rate of 200 microgram/kg of body weight by IV (n = 12) or IM injection (n = 12) or given as an oral paste (n = 12). Ponies were euthanatized and necropsied 21 days after treatment. In each nontreated or vehicle-treated pony, late lst-, lst- to 2nd-instar molt, and early 2nd-instars of G intestinalis were found in the mouth, and 2nd- and 3rd instars of G intestinalis and 3rd instars of G nasalis were found in the stomach. Bots were not found in any ivermectin-treated pony and, thus, ivermectin was 100% effective against oral and gastric stages. Adverse reactions were not observed in ponies given ivermectin by IM injection or orally, but 1 pony given the vehicle IV and 1 pony given ivermectin (in the vehicle) IV had an anaphylactic reaction, resulting in death of the ivermectin-treated pony. It was speculated that the adverse reaction was caused by histamines released in response to vehicle components given by IV injection.

A controlled anthelmintic trial was conducted to determine the efficacy of febantel paste (45.5%) at dosages of 2.5, 5.0, 7.5, and 10.0 mg/kg in calves harboring natural gastrointestinal nematode infections. Dosages of 5.0, 7.5 and 10.0 mg of febantel/kg of body weight were greater than 96% effective in removing adults of Haemonchus contortus, Ostertagia spp, Cooperia spp, and Oesophagostomum radiatum. The 2.5 mg/kg dosage was considered suboptimal because of low efficacy against Ostertagia and Cooperia spp. Efficacies against Trichostrongylus axei, Trichuris spp, Bunostomum phlebotomum, and Strongyloides papillosus were difficult to determine because fewer numbers of these nematodes were recovered. Efficacies of febantel paste against immature bovine parasites ranged from 83.62% to 97.72%.

The disposition of theophylline in healthy ruminating calves was best described by a first-order 2-compartment open pharamacokinetic model. The drug had a mean elimination half-life of 6.4 hours and a mean distribution half-life of 22 minutes. Total body clearance averaged 91 ml/kg/h. The mean values for the pharmacokinetic volume of the central compartment, pharmacokinetic volume of distribution during the terminal phase, and volume of distribution at steady state were 0.502, 0.870, and 0.815 L/kg, respectively. Theophylline was readily absorbed after oral administration to the ruminating calf, with a mean fraction of 0.93 absorbed. The plasma concentrations after oral dosing peaked in approximately 5 to 6 hours, with a mean absorption half-life of 3.7 hours. A flip-flop model (rate constant of input is much smaller than the rate constant of output) of drug absorption was not found because the elimination process roughly paralleled that of the study concerning IV administration. In a multiple-dose trial that used a dosage regimen based on single-dose pharmacokinetic values, clinically normal calves responded as predicted. However, diseased calves had higher than expected plasma concentrations after being given multiple oral doses of theophylline at 28 mg/kg once daily. Overt signs of toxicosis were not seen, but this aspect of the drug was not formally investigated. Theophylline can be used as an ancillary therapeutic agent to treat bovine respiratory disease, but not without risk. The suggested oral dose of theophylline at 28 mg/kg of body weight once daily should be tailored to each case. Twice daily oral dosing at 20 mg/kg should reduce the plasma peak:trough ratio and provide plasma concentrations more cnsistently within the human therapeutic range of 10 to 20 micrograms/ml. Even then, therapeutic drug monitoring should be done.

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).

peer reviewed | OBJECTIVE: To evaluate the effects of using ropivacaine combined with dexmedetomidine for sciatic and saphenous nerve blocks in dogs. ANIMALS: 7 healthy adult Beagles. PROCEDURES: In phase 1, dogs received each of the following 3 treatments in random order: perineural sciatic and saphenous nerve injections of 0.5% ropivacaine (0.4 mL/kg) mixed with saline (0.9% NaCl) solution (0.04 mL/kg; DEX0PN), 0.5% ropivacaine mixed with dexmedetomidine (1 μg/kg; DEX1PN), and 0.5% ropivacaine mixed with dexmedetomidine (2 μg/kg; DEX2PN). In phase 2, dogs received perineural sciatic and saphenous nerve injections of 0.5% ropivacaine and an IV injection of diluted dexmedetomidine (1 μg/kg; DEX1IV). For perineural injections, the dose was divided equally between the 2 sites. Duration of sensory blockade was evaluated, and plasma dexmedetomidine concentrations were measured. RESULTS: Duration of sensory blockade was significantly longer with DEX1PN and DEX2PN, compared with DEX0PN; DEX1IV did not prolong duration of sensory blockade, compared with DEX0PN. Peak plasma dexmedetomidine concentrations were reached after 15 minutes with DEX1PN (mean ± SD, 348 ± 200 pg/mL) and after 30 minutes DEX2PN (816 ± 607 pg/mL), and bioavailability was 54 ± 40% and 73 ± 43%, respectively. The highest plasma dexmedetomidine concentration was measured with DEX1IV (1,032 ± 415 pg/mL) 5 minutes after injection. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that perineural injection of 0.5% ropivacaine in combination with dexmedetomidine (1 μg/kg) for locoregional anesthesia in dogs seemed to balance the benefit of prolonging sensory nerve blockade while minimizing adverse effects.

Objective-To measure effects of Escherichia coli O149:F4-induced diarrhea on water consumption and pharmacokinetics of amoxicillin after administration in drinking water. Animals-24 recently weaned 24- to 28-day-old crossbred pigs. Procedure-10 pigs were inoculated with E coli O149:F4; all 10 pigs subsequently developed diarrhea. Pigs were medicated by administration of amoxicillin in the drinking water (0.75 mg/mL) for a 4-hour period on 2 consecutive days. Fourteen age-matched noninfected healthy pigs (control group) were medicated in a similar manner. Blood samples were obtained from both groups daily, and plasma concentrations of amoxicillin were analyzed by use of high-performance liquid chromatography. Results-Diarrhea reduced the area under the plasma concentration-versus-time curve (AUC) and maximum plasma concentration (C(max)) of amoxicillin on the first day of medication by 56% and 63%, respectively. The AUC of amoxicillin on the second day of medication for diarrheic pigs did not differ significantly from that of control pigs on the first day of medication. Conclusions and Clinical Relevance-E coli-induced diarrhea reduced the AUC of amoxicillin and time that plasma concentration of amoxicillin was > 0.025 microgram/mL and, hence, less likely to have a therapeutic effect on the first day of administration in drinking water. On the assumption that plasma concentrations may indirectly reflect concentrations at the site of infection, analysis of our results suggests that higher doses of amoxicillin may be appropriate for administration in drinking water during a 4-hour period on the first day that pigs have diarrhea attributable to E coli O149:F4.

The role of interleukin 1 (IL-1) as an inflammatory mediator during mastitis and the therapeutic effect of recombinant human IL-1 receptor antagonist (IL-1ra) for bovine mastitis was studied. Cows were intramammarily infused with lipopolysaccharide (25 g) in 1 mammary gland. Half the cows also received infusions of 5 mg of IL-1ra into the same mammary gland just prior to endotoxin infusion and 4, 8, and 12 hours later. After endotoxin infusion, tumor necrosis factor and high IL-1 bioactivity were detected in whey from infused glands. Vascular permeability changes and neutrophil accumulation in milk paralleled the appearance of cytokines. A systemic reaction, characterized by pyrexia and an increase in blood cortisol concentration, also were observed. Milk yield was inhibited and milk composition was altered in infused and noninfused glands. The increase in IL-1 bioactivity in milk after endotoxin infusion was almost completely prevented in glands receiving IL-1ra. However, IL-1ra had no effect on local inflammation, systemic reaction, or impairment in productive performance. These results indicate that IL-1 does not mediate its effect within the milk compartment, and suggest either that IL-1 is not critical to the mastitic response or that intramammary infusion of IL-1ra does not place the antagonist where IL-1 interacts with its receptor.

A cross-over study was performed in 6 healthy mixed-breed dogs and 4 healthy Beagles. Diazepam was administered per rectum to Beagles (0.5 mg/kg of body weight) and mixed-breed dogs (2 mg/kg), and IV (0.5 mg/kg) to both groups of dogs. Each dog received the drug by both routes, with a 1-week washout period between dosages. After diazepam administration, blood samples were collected to measure plasma concentration of diazepam and its active metabolites, desmethyldiazepam and oxazepam, by use of reverse-phase high-performance liquid chromatography (HPLC). Systemic availability was assessed by comparing the area under the curve for diazepam metabolites for each route of administration. Mean (+/- SD) diazepam concentrations in plasma after rectal administration were low in comparison with those obtained after IV administration, with systemic availability of only 7.4 (+/- 5.9) and 2.7 (+/- 3.2)% for the high and low dose, respectively. However, diazepam was converted to its metabolites within minutes after administration. Accounting for the total concentration of benzodiazepines (diazepam plus desmethyldiazepam and oxazepam) in plasma, systemic availability was 79.9 (+/- 20.7) and 66.0 (+/- 23.8)% for the high and low dosage, respectively. After IV administration, diazepam concentration decreased, with a half-life of only 14 to 16 minutes, but desmethyldiazepam and oxazepam concentrations decreased more slowly, with a half-life of 2.2 to 2.8 hours and 3.5 to 5.1 hours, respectively. Each of the metabolites is reported to have anticonvulsant activity. After rectal administration of the high dose, mean total benzodiazepine concentration was above 1.0 micrograms/ml within 10 minutes and was maintained above this concentration for at least 6 hours. We conclude that diazepam is absorbed after rectal administration in dogs, and that the pharmacologic effects are probably caused by the active metabolites, not the parent drug. Samples also were analyzed by use of a nonspecific commercial benzodiazepine fluorescence polarization immunoassay (FPIA). Correlation between the FPLA and HPLC assay was strongest for diazeparn (R2 = 0.84), weak for desmethyldiazepam (R2 = 0.09), and nonexistent for oxazepam. We conclude from a comparison of assays that HPLC is preferred over the FPLA method for measuring benzodiazepines in dogs.

Consumption of chlortetracycline (CTC) at concentration of 220 mg/kg of feed for 4 weeks in experiment 1 and at concentrations of 110 and 220 mg/kg for 3 weeks and 440 mg/kg for 2 weeks in experiment 2 failed to eliminate streptococci-induced lymphadenitis from swine referred to as principals. Abscesses, mostly in the head and neck, developed in at least a third of all swine in the various groups fed these CTC concentrations. Feeding of 220 mg of CTC/kg of feed in experiment 1 began 12 weeks after exposure of principals to an untypeable group E streptococci (GES; isolate 3X29A). In experiment 2, feeding of 110 and 220 mg of CTC/kg of feed began 5 weeks after exposure of principals to GES and feeding of 440 mg of CTC/kg of feed began 6 weeks after exposure. One or more cohabitating sentinel swine of experiment 1 and one or more sentinels in all groups of principals of experiment 2, except group 2, developed abscesses that were mostly in the head and neck. In experiment 2, correlation between serum GES antibody titer and development of one or more abscesses in the principals was highly significant (P < 0.01); however, correlation between antibody titer and abscesses in the sentinels only approached significance (P < 0.10).