Search

This guideline is intended as an aid in the design, implementation and interpretation of studies for the assessment of drug efficacy against Eimeria in cattle and sheep, Cystoisospora in pigs and dogs, and Cryptosporidium in cattle. It deals with the most important aspects of how to conduct both experimental and field studies for dose determination, dose confirmation and assessment of field effectiveness. Also, guidance on the selection of animals, diagnostic techniques, statistical evaluation and methods for the preparation, maintenance and use of parasites is provided. The specific management conditions that may influence the course of natural infections and consequently determine treatment schemes are mentioned and suggestions for best practice in sampling and evaluation of data prior to conducting of efficacy studies are given. The guideline is also intended to assist investigators in carrying out specific studies, provide relevant information for registration authorities involved in the decision-making process, assist in the approval of anticoccidial drugs in the target species, and facilitate the world-wide adoption of standard procedures. Although currently not implemented, issues of drug resistance testing and alternative methods for drug testing are also discussed as future issues in drug testing against mammalian coccidia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Experimental infections are required by current guidelines for investigating the efficacy of anthelmintics in dogs and cats. Recently, alternatives to experimental infections and the sacrificing of research dogs and cats have been evaluated, and novel conceptual investigations and methods of examination have been explored. Several of these approaches could potentially be used in efficacy studies for anthelmintics in dogs and cats. Here, we provide food for thought towards using new tools for evaluating the efficacy of anthelmintics in companion animals, for promoting the value of field trials, and for updating the existing guidelines for the efficacy testing of anthelmintics in dogs and cats., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

In Ontario, Canada, widespread resistance to ivermectin and fenbendazole, the only readily available ovine anthelmintics, has been documented, primarily in Haemonchus sp. In other parts of the world, closantel has been used to control such infections; however, the drug was not currently licensed for use in Canada and the USA. A randomized controlled trial was conducted on six client-owned farms in Ontario in 2013 and 2014 to determine the efficacy of closantel (Flukiver ® 5% Oral Suspension, Elanco Animal Health, 10mg/kg bodyweight) against ivermectin- and fenbendazole-resistant Haemonchus sp. infections in periparturient ewes and grazing lambs. Three farms were randomly assigned to treat all ewes, and three farms were randomly assigned to selectively treat individual ewes at lambing, using predetermined criteria. Fecal samples were collected from a minimum of 15 randomly selected ewes and 13 lambs per group on each farm at the time of treatment and approximately 14days later. Trichostrongyle-type fecal egg counts (FEC) were performed using a modified McMaster technique with a lower detection limit of 8.3 eggs per gram of feces (epg). Haemonchus-specific FECs were determined by multiplying FECs by the proportion of Haemonchus sp. identified from coproculture for each farm; Haemonchus-specific FEC reductions were calculated for each farm. Twenty grazing lambs had FECs conducted monthly, and when mean monthly FECs surpassed 200 epg, all lambs were randomly allocated to either closantel, positive control (ivermectin, fenbendazole, or levamisole) or negative control groups. Pre-treatment Haemonchus-specific mean FECs ranged from 27 to 3359 epg in ewes and 0-5698 epg in lambs. Efficacy of closantel against Haemonchus sp. ranged from 99% (95% CI: 97%-99%) to 100% in recently lambed ewes on all farms in both years (total n=274 ewes), and from 99% (95% CI: 98%-99%) to 100% in grazing lambs in both years on all but one farm (total n=171 lambs). On the latter farm, a whole flock treated farm, closantel efficacy in grazing lambs was 84% (95%CI: 81%-88%) in the first year, but 100% in the second year. Levamisole was effective against overall GIN in lambs on only two farms. Ivermectin and fenbendazole resistance continued to be present, particularly in Haemonchus sp. Closantel had excellent efficacy against Haemonchus sp. over the two year study period, regardless of treatment group, and therefore should be considered one viable component of sustainable integrated parasite control programs for farms with documented anthelmintic resistance and problems with haemonchosis., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Fluralaner is a new antiparasitic drug that was recently introduced as Bravecto chewable tablets for the treatment of tick and flea infestations in dogs. Most marketed tick products exert their effect via topical application and contact exposure to the parasite. In contrast, Bravecto delivers its acaricidal activity through systemic exposure. Tick exposure to fluralaner occurs after attachment to orally treated dogs, which induces a tick-killing effect within 12 h. The fast onset of killing lasts over the entire treatment interval (12 weeks) and suggests that only marginal uptake by ticks is required to induce efficacy. Three laboratory studies were conducted to quantify the extent of uptake by comparison of ticks' weight and coxal index obtained from Bravecto-treated and negative-control dogs., Methods: Three studies were conducted using experimental tick infestation with either Ixodes ricinus or Ixodes scapularis after oral administration of fluralaner to dogs. All studies included a treated (Bravecto chewable tablets, MSD Animal Health) and a negative control group. Each study had a similar design for assessing vitality and weighing of ticks collected from dogs of both groups. Additionally, in one study the coxal index (I. ricinus) was calculated as a ratio of tick's ventral coxal gap and dorsal width of scutum. Tick weight data and coxal indices from Bravecto-treated and negative-control groups were compared via statistical analysis., Results: Ticks collected from Bravecto-treated dogs weighed significantly less (p ≤ 0.0108) than ticks collected from negative-control dogs, and their coxal index was also significantly lower (p < 0.0001). The difference in tick weights was demonstrated irrespective of the tick species investigated (I. ricinus, I. scapularis). At some assessments the mean tick weights of Bravecto-treated dogs were significantly lower than those of unfed pre-infestation (baseline) ticks. The demonstrated tick-killing efficacy was in the range of 94.6 - 100%., Conclusions: Tick weights and coxal indices confirm that a minimal uptake results in a sufficient exposure of ticks to fluralaner (Bravecto) and consequently in a potent acaricidal effect.

Background: Ctenocephalides canis is a major flea species in dogs in several European countries. The new topical combination of fipronil and permethrin (Frontline Tri-Act/Frontect, Merial) has been developed to control fleas, ticks, mosquitoes, sandflies and biting flies on dogs. Considering the repellent and insecticidal effects of permethrin and the insecticidal effect of fipronil, the efficacy of the combination against fleas including C. canis was expected to be rapid. The study was conducted to measure the 1-hour, 6-hour and 24-hour efficacy, as well as the repellent activity, of the fipronil-permethrin combination on treated versus untreated dogs., Methods: 12 Beagle dogs were randomly allocated to one of two groups based on pre-treatment live flea counts. Dogs in Group 1 remained untreated whereas dogs in Group 2 were treated once on Day 0. Each dog was infested with 100 unfed adult C. canis on Days 2, 7, 14, 21 and 28. Dogs were combed for fleas 1 and 6 h after each infestation. Following this examination, fleas remaining on the liner at the bottom of each cage were collected and counted. All live fleas were placed back on each dog after the 1- and 6-hour counts. A comb-count was performed at 24 h post infestation on all dogs., Results: Treated dogs had significantly (p ≤ 0.01) lower flea counts than untreated dogs at every time point. The percent efficacy was ≥99.1% at 6 and 24 h after each weekly challenge up to the month. The 1-hour counts also showed good efficacy of 96.5%, 98.9%, 92.0%, 70.2% and 55.7% on Days 2, 7, 14, 21 and 28, respectively. The repellent efficacy, assessed on the liners at 1 h, was 86.5%, 94.9%, 79.5%, 58.4% and 43.9% on Days 2, 7, 14, 21 and 28, respectively., Conclusions: This study demonstrates the beneficial effect of the fipronil and permethrin combination against C. canis, providing both a repellent and insecticidal effect as early as 1 h post infestation, and >99.1% efficacy calculated at 6 h during a month.

Background: Two blinded, controlled laboratory studies were conducted to assess the acaricidal efficacy of a new combination of fipronil and permethrin (Frontline Tri-Act/Frontect) against two tick species. Study A evaluated the efficacy of the product against both Ixodes ricinus and Rhipicephalus sanguineus and Study B evaluated the efficacy against R. sanguineus only., Methods: 16 (Study A) and 12 (Study B) healthy adult dogs were allocated to two groups in each study. Dogs in Group 1 served as untreated controls. Dogs in Group 2 were treated with a new topical spot-on formulation containing 6.76% (w/v) fipronil + 50.48% (w/v) permethrin once on Day 0. Each dog of study A was infested with 50 unfed adult ticks of each species and each dog of study B was infested with 50 unfed adult Rhipicephalus sanguineus prior to treatment (Day -2 in Study A, Day -1 in Study B) and post treatment on Days 7, 14, 21 and 28. The ticks were removed and counted 48 h after treatment (Day 2) or subsequent infestations (Days 9, 16, 23 and 30). Acaricidal efficacy was defined as the percent reduction in the number of live ticks in the treated group compared to the untreated control group., Results: The percent efficacy in the treated group for R. sanguineus was 100%, 100%, 100%, 100% and 96.7% in Study A, and 94.4%, 100%, 100%, 98.7% and 98.0% in Study B, for counts performed on Days 2, 9, 16, 23 and 30, respectively. For I. ricinus, in Study A, the percent efficacy of the treatment was 100%, 100%, 100%, 100% and 99.2% for counts performed on Days 2, 9, 16, 23 and 30, respectively. There was a significant difference of the geometric mean numbers of live ticks between the treated and control groups at each time point in each study (p = 0.005 for every day in Study A, and p < 0.005 for every day in Study B)., Conclusions: A single topical administration of a combination of fipronil and permethrin provides excellent acaricidal efficacy against both I. ricinus and R. sanguineus for at least 4 weeks.

Objective: To determine the optimal method for use of the Canine Brief Pain Inventory (CBPI) to quantitate responses of dogs with osteoarthritis to treatment with carprofen or placebo., Animals: 150 dogs with osteoarthritis., Procedures: Data were analyzed from 2 studies with identical protocols in which owner-completed CBPIs were used. Treatment for each dog was classified as a success or failure by comparing the pain severity score (PSS) and pain interference score (PIS) on day 0 (baseline) with those on day 14. Treatment success or failure was defined on the basis of various combinations of reduction in the 2 scores when inclusion criteria were set as a PSS and PIS ≥ 1, 2, or 3 at baseline. Statistical analyses were performed to select the definition of treatment success that had the greatest statistical power to detect differences between carprofen and placebo treatments., Results: Defining treatment success as a reduction of ≥ 1 in PSS and ≥ 2 in PIS in each dog had consistently robust power. Power was 62.8% in the population that included only dogs with baseline scores ≥ 2 and 64.7% in the population that included only dogs with baseline scores ≥ 3., Conclusions and Clinical Relevance: The CBPI had robust statistical power to evaluate the treatment effect of carprofen in dogs with osteoarthritis when protocol success criteria were predefined as a reduction ≥ 1 in PIS and ≥ 2 in PSS. Results indicated the CBPI can be used as an outcome measure in clinical trials to evaluate new pain treatments when it is desirable to evaluate success in individual dogs rather than overall mean or median scores in a test population.

Background: Two studies were conducted to evaluate and compare the efficacy of imidacloprid + moxidectin and selamectin topical solutions against the KS1 flea strain infesting cats. In both studies the treatment groups were comprised of non-treated controls, 6% w/v selamectin (Revolution®; Pfizer Animal Health) topical solution and 10% w/v imidacloprid + 1% w/v moxidectin (Advantage Multi® for Cats, Bayer Animal Health) topical solution. All cats were infested with 100 fleas on Days -2, 7, 14, 21, and 28. The difference in the studies was that in study #1 efficacy evaluations were conducted at 24 and 48 hours post-treatment or post-infestation, and in study #2 evaluations were conducted at 12 and 24 hours., Results: In study #1 imidacloprid + moxidectin and the selamectin formulation provided 99.8% and 99.0% efficacy at 24 hours post-treatment. On day 28, the 24 hour efficacy of the selamectin formulation dropped to 87.1%, whereas the imidacloprid + moxidectin formulation provided 98.9% efficacy. At the 48 hour assessments following the 28 day infestations, efficacy of the imidacloprid + moxidectin and selamectin formulations was 96.8% and 98.3% respectively. In study # 2 the efficacy of the imidacloprid + moxidectin and selamectin formulations 12 hours after treatment was 100% and 69.4%, respectively. On day 28, efficacy of the imidacloprid + moxidectin and selamectin formulations 12 hours after infestation was 90.2% and 57.3%, respectively. In study #2 both formulations provided high levels of efficacy at the 24 hour post-infestation assessments, with selamectin and imidacloprid + moxidectin providing 95.3% and 97.5% efficacy, following infestations on day 28., Conclusions: At the 24 and 48 hour residual efficacy assessments, the imidacloprid + moxidectin and selamectin formulations were similarly highly efficacious. However, the imidacloprid + moxidectin formulation provided a significantly higher rate of flea kill against the KS1 flea strain infesting cats at every 12 hour post-infestation residual efficacy assessment. Both formulations should provide excellent flea control for an entire month on cats.

Active immunization against pro-angiogenic growth factors or their receptors is an emerging strategy for controlling tumor growth and angiogenesis. Previous studies in rodent tumor models have indicated that immunization against xenogeneic growth factors is more likely to induce effective anti-tumor responses than immunization against the autologous growth factor. However, the effectiveness or safety of the xenogeneic vaccination approach has not been previously assessed in a clinically relevant outbred, spontaneous tumor model. Therefore, we investigated the safety and anti-tumor and anti-angiogenic effects of a xenogeneic vascular endothelial cell growth factor (VEGF) vaccine in pet dogs with spontaneous cancer. Nine dogs with soft tissue sarcoma were immunized with a recombinant human VEGF vaccine over a 16-week period. The effects of immunization on antibodies to human and canine VEGF, circulating VEGF concentrations, tumor microvessel density (MVD), and tumor growth were assessed. The xenogeneic VEGF vaccine was well-tolerated by all dogs and resulted in induction of humoral responses against both human and canine VEGF in animals that remained in the study long enough to receive multiple immunizations. Three of five multiply immunized dogs also experienced sustained decreases in circulating plasma VEGF concentrations and two dogs had a significant decrease in tumor MVD. The overall tumor response rate was 30% for all treated dogs in the study. We conclude therefore that a xenogeneic VEGF vaccine may be a safe and effective alternative means of controlling tumor growth and angiogenesis.

Objective: To evaluate the efficacy of a single injection of a sustained-release formulation of moxidectin in preventing heartworm (Dirofilaria immitis) infection for 12 months in dogs., Animals: 14 healthy dogs., Procedure: Group A (nontreated control dogs; n = 6) received sterile vehicle administered SC, and group B (treated dogs; n = 6) received a sustained-release formulation of moxidectin administered SC. All dogs were housed in a heartworm-endemic area for 11.5 months, and heartworm antigen and modified Knott tests were performed monthly. All dogs (including 2 additional control dogs [group C]) were then inoculated with infective-stage larvae (L3) of D. immitis, and 4.5 months later, all dogs were euthanatized and post-mortem examinations were performed. Adult D. immitis were counted and measured, and their age was estimated., Results: All dogs in groups A and C were infected with young (4- to 4.5-month old) adult male and female D. immitis. No dogs in group B were infected with heartworms. CONCLUSIONS AND., Clinical Relevance: The age of heartworms recovered suggests that infection was the result of experimental inoculation and not natural exposure to mosquitoes during the 11.5-month period the dogs resided in a heartworm-endemic area. A single SC injection of a sustained-release formulation of moxidectin was effective in providing protection against heartworm infection after 12 months in dogs. This formulation is a convenient method of heartworm prophylaxis that could eliminate the problem of poor owner compliance.

These guidelines have been written to aid in the design, implementation and interpretation of studies for the assessment of drug efficacy against Eimeria species in chickens and turkeys. The information provided deals with many aspects of how to conduct controlled studies in battery cages (dose determination), floor pens (dose confirmation), and commercial facilities (field effectiveness studies), the selection of birds, housing, feeding, preparation of medicated rations, record keeping, diagnostic techniques, and methods for the preparation, maintenance and use of parasites. These guidelines are also intended to assist investigators in conducting specific studies, provide specific information for registration authorities involved in the decision-making process, assist in the approval and registration of new anticoccidial drugs, and facilitate the world-wide adoption of standard procedures.

Objective: To determine the maximum tolerated dose (MTD) of cisplatin administered with piroxicam, the antitumor activity and toxicity of cisplatin combined with piroxicam in dogs with oral malignant melanoma (OMM) and oral squamous cell carcinoma (SCC), and the effects of piroxicam on the pharmacokinetics of cisplatin in dogs with tumors., Design: Prospective nonrandomized clinical trial., Animals: 25 dogs., Procedure: Dogs were treated with a combination of cisplatin (escalating dose with 6 hours of diuresis with saline [0.9% NaCI] solution) and piroxicam (0.3 mg/kg 10.14 mg/lb], PO, q 24 h). The initial cisplatin dose (50 mg/m2) was increased by 5 mg/m2 until the MTD was reached. Tumor stage and size were determined at 6-week intervals during treatment. The pharmacokinetics of cisplatin were determined in dogs receiving a combination of cisplatin and piroxicam during the clinical trial and dogs that were treated with cisplatin alone., Results: 11 dogs with OMM and 9 dogs with SCC were included in the clinical trial. The MTD of cisplatin when administered in combination with piroxicam was 50 mg/m2. Tumor remission occurred in 5 of 9 dogs with SCC and 2 of 11 dogs with OMM. The most common abnormality observed was renal toxicosis. Clearance of cisplatin in dogs that were treated with cisplatin alone was not significantly different from that in dogs treated with a combination of cisplatin and piroxicam., Conclusions and Clinical Relevance: Cisplatin administered in combination with piroxicam had antitumor activity against OMM and SCC. The level of toxicity was acceptable, although renal function must be monitored carefully.

These guidelines have been prepared to assist in the planning, operation and interpretation of studies designed to assess the effectiveness of drugs against helminth parasites of chickens and turkeys. They are the first to be compiled under the auspices of the World Association for the Advancement of Veterinary Parasitology (WAAVP) for these parasites. The advantages and disadvantages of the widely used critical and controlled tests are discussed. Information is provided on the selection of animals for experiments, animal housing, feed, dose determination studies, confirmatory and field trials, record keeping and necropsy procedures. This document should help investigators and those involved in product approval and registration in conducting and evaluating studies concerned with determining the effectiveness and safety of anthelmintic drugs.

A thermal analgesiometric device was developed for unrestrained cats. Heat was provided by an electrical element potted together with a temperature sensor in thermally conductive epoxy in a 5 gm probe. This was attached to an elasticated band round the cat's thorax with an inflated bladder maintaining constant pressure between probe and skin. A safety cut-off was set at 60 degrees C. End point was a skin flick, turning, or jumping. Threshold temperatures in untreated cats were around 40 degrees C and repeatable to 4 degrees C with 5, 10 or 15 minutes between tests. Threshold temperature was stable in tests at 15 minutes intervals without false positives or negatives. Tests repeated at weekly intervals were repeatable to within 4 degrees C. Treatment with the opioid analgesic pethidine increased the threshold temperatures 10.2 (6.7) degrees C 45 minutes after treatment. The device was well tolerated for at least 24 hours and the analgesic effect of an opioid was detected. The system appears suitable for use in investigations into analgesic pharmacology in cats., (Copyright 2002 Elsevier Science Ltd. All rights reserved.)

The aims of this investigation were to calculate the pharmacokinetic parameters and to identify parameters, based on individual plasma concentration-time curves of amoxicillin and clavulanic acid in cats, that may govern the observed differences in absorption of both drugs. The evaluation was based on the data from plasma concentration-time curves obtained following a single-dose, open, randomised, two-way crossover phase-I study, each involving 24 female cats treated with two Amoxi-Clav formulations (formulation A was Clavubactin and formulation was B Synulox; 80/20 mg, 24 animals, 48 drug administrations). Plasma amoxicillin and clavulanic acid concentrations were determined using validated bioassay methods. The half-life of elimination of amoxicillin is 1.2 h (t1/2 = 1.24 +/- 0.28 h, Cmax = 12.8 +/- 2.12 microg/ml), and that of clavulanic acid 0.6 h (t1/2 = 0.63 +/- 0.16 h, Cmax = 4.60 +/- 1.68 microg/ml). There is a ninefold variation in the AUCt of clavulanic acid for both formulations, while the AUCt of amoxicillin varies by a factor of two. The highest clavulanic acid AUCt values indicate the best absorption; all other data indicate less absorption. Taking into account that the amoxicillin-to-clavulanic acid dose ratio in the two products tested was 4:1, the blood concentration ratios may actually vary much more, apparently without compromising the products" high efficacy against susceptible microorganisms.

These guidelines have been designed to assist in the planning, operation and interpretation of studies which would serve to assess the efficacy of drugs against internal parasites of horses. Although the term anthelmintic is used in the title and text, these guidelines include studies on drug efficacy against larvae of horse bot flies, Gasterophilus spp., which are non-helminth parasites commonly occurring in the stomach of horses. The advantages, disadvantages and application of critical and controlled tests are presented. Information is also provided on selection of animals, housing, feed, dose titration, confirmatory and clinical trials, record keeping and necropsy procedures. These guidelines should assist both investigators and registration authorities in the evaluation of compounds using comparable and standard procedures with the minimum number of animals.

Objective: To evaluate the use of piroxicam for the treatment of oral squamous cell carcinoma in dogs., Design: Prospective case series., Animals: 17 dogs with measurable oral squamous cell carcinoma., Procedure: Dogs were treated with piroxicam at a dosage of 0.3 mg/kg (0.14 mg/lb) of body weight, PO, every 24 hours until progressive disease or unacceptable signs of toxicosis developed or the dog died., Results: One dog had a complete remission (maxillary tumor), and 2 dogs had partial remissions (lingual tumor and tonsillar tumor). An additional 5 dogs had stable disease, including 1 with a maxillary tumor, 2 with mandibular tumors, and 2 with tonsillar tumors. Variables associated with tumor response were not identified. Median and mean times to failure for the 3 dogs that had a remission were 180 and 223 days, respectively. Median and mean times to failure for the 5 dogs with stable disease were 102 and 223 days, respectively. Time to failure was positively associated with tumor response and negatively associated with tumor size. One dog had mild adverse gastrointestinal tract effects that resolved with the addition of misoprostol to the treatment regimen., Conclusions and Clinical Relevance: Results suggest that piroxicam may be useful in the treatment of dogs with oral squamous cell carcinoma; response rate was similar to that reported for other cytotoxic treatments. Larger-scale studies are warranted to determine what role piroxicam may have, alone or in combination with other treatments, for the treatment of dogs with oral squamous cell carcinoma.

Objective: To compare toxicokinetic variables and associated tissue drug concentrations with severity of articular lesions in weight-bearing joints of juvenile rabbits after oral administration of a fluoroquinolone., Animal: Ten 6- to 7-week-old, 800- to 1,200-g, New Zealand White rabbits., Procedures: Rabbits were gavaged daily with the fluoroquinolone PD 117596 at 500 mg/kg of body weight for 5 days. Blood samples were collected on day 4 at preestablished times, up to 24 hours after drug administration. On day 5 gross lesion severity and prevalence were evaluated in the major weight-bearing joints, and tissue specimens were collected (60 minutes after drug administration). Serum and tissue drug concentrations were determined by microbiologic plate assay., Results: Macroscopically, treatment rabbits had a high prevalence of arthropathy with the distal portion of the femur having the highest prevalence and severity of lesions. Grossly, alterations to articular cartilage included 1 to 4 mm in diameter vesicles or erosions. Histologically, vesicles were identified in the midzone or close to the zone of calcified cartilage of treatment rabbits. Chondrocyte cellularity was reduced in affected areas, and perivesicular regions had reduced staining with Safranin O. Correlation analysis of area under the curve values with total scores for lesion severity had a significant positive relationship., Conclusions: Our findings support the use of juvenile rabbits as a model for arthropathic changes induced by fluoroquinolone administration.

Objective: To evaluate the safety of sodium bisulfate for use in horse barn environments by determining its irritant effect on skin and hooves., Animals: 6 female mixed-breed ponies., Procedure: Sodium bisulfate was applied to clipped intact skin of 6 ponies to evaluate its irritant effect after single (48 hours) and repetitive (6 h/d for 10 days) applications; similar areas of skin were used as untreated control sites. In addition, sodium bisulfate was applied to the sole of both front hooves of each pony and covered with wet gauze, and the entire hoof was covered with adhesive tape for 48 hours., Results: Contact with moistened sodium bisulfate for 48 hours had no effect on pony skin. Contact with sodium bisulfate for 6 hours on 10 consecutive days did not cause gross changes but did cause mild to moderate microscopic changes including epidermal necrosis, hyperkeratosis, capillary congestion, edema, and diffuse mixed inflammatory cell infiltrate. All changes were limited to the epidermis and superficial dermis. Gross changes in hoof sole, signs of lameness, and increase in digital pulse pressure or pulse intensity were not detected., Conclusions and Clinical Relevance: Duration of contact with sodium bisulfate in this study was in excess of that expected under typical husbandry conditions. Despite this fact, gross changes in skin and hooves were not detected. Microscopic lesions were confined to the epidermis and superficial dermis. Results suggest that contact with sodium bisulfate under these conditions is safe.

The efficacy of a florfenicol premix was studied in weaning pigs experimentally inoculated with Actinobacillus pleuropneumoniae. Twenty five clinically healthy pigs were distributed into 3 groups; group A non-medicated, groups B and C orally medicated with 20 and 40 ppm of florfenicol respectively. The pigs were fed during 12 consecutive days and on day 5 all the groups were challenged with A. pleuropneumoniae serotype 1. All the animals in Group A developed clinical signs. Most of the pigs in the medicated groups maintained a good health status. Postmortem examination revealed severe pleuropneumonia in pigs from the control group and pneumonic lesions in 40% of the animals treated with 20 ppm of florfenicol. Development of pleuropneumonia was prevented in all the pigs medicated with 40 ppm of florfenicol. Actinobacillus pleuropneumoniae was recovered from the lungs of all control animals and from one pig of each of the medicated groups, however, the avidin biotin peroxidase (ABC-P) method detected the presence of the microorganism in all the animals. We demonstrated that medication with feed containing 40 ppm of florfenicol blocked efficiently the signs and lesions caused by A. pleuropneumoniae and increased the daily body weight gain.

Objective: To determine pharmacokinetic parameters of thiamphenicol (TAP) after IV and IM administration in dogs., Animals: 6 healthy 2- to 3-year-old male Beagles., Procedure: IN a crossover design study, 3 dogs were given TAP IV, and 3 dogs were given TAP IM, each at a dosage of 40 mg/kg of body weight. Three weeks later, the same dogs were given a second dose by the opposite route. At preestablished times after TAP administration, blood samples were collected through a catheter placed in the cephalic vein, and TAP concentration was determined by use of a high-performance liquid chromatography. Results-Kinetics of TAP administered IV were fitted by a biexponential equation with a rapid first disposition phase followed by a slower disposition phase. Elimination half-life was short (1.7+/-0.3 hours), volume of distribution at steady state was 0.66+/-0.05 L/kg, and plasma clearance was 5.3+/-0.7 ml/min/kg. After IM administration, absorption was rapid. Peak plasma concentration (25.1+/-10.3 microg/ml) was reached about 45 minutes after drug administration. The apparent elimination half-life after IM administration (5.6+/-4.6 hours) was longer than that after IV administration probably because of the slow absorption rate from the muscle. Mean bioavailability after IM administration was 96+/-7%., Conclusion: The pharmacokinetic profile of TAP in dogs suggests that it may be therapeutically useful against susceptible microorganisms involved in the most common infections in dogs, such as tracheobronchitis, enterocolitis, mastitis, and urinary tract infections.

Objective: To evaluate the effect on intramuscular blood flow (IMBF) and hemodynamic variables of 4 antihypotensive agents given during anesthesia., Animals: 8 ponies., Procedure: Halothane-anesthetized ponies (n = 6) positioned in lateral recumbency received, on separate occasions, infusions of each of the following 4 agents in serially increasing dosages or saline solution: phenylephrine hydrochloride (0.25, 0.5, 1, and 2 microg/kg of body weight), dopamine (2.5, 5, 10, and 20 microg/kg), dobutamine (1, 2.5, 5, and 10 microg/kg), and dopexamine (0.5, 1, 5, and 10 microg/kg). Changes in IMBF (by laser-Doppler flowmetry) in nondependent and dependent triceps brachii muscles and cardiopulmonary variables were measured., Results: Phenylephrine at all dosages failed to improve IMBF or cardiac index (CI), but increased mean arterial pressure (MAP) and systemic vascular resistance (SVR); 2 ponies had forelimb lameness on recovery. Dopamine (10 microg/kg/min) increased CI, MAP, and IMBF in the dependent muscle. A higher dose (20 microg/kg/min) caused cardiac arrhythmias and muscular tremor. Dobutamine increased Cl, MAP, and IMBF of both forelimbs, effects being significant for 2.5 microg/kg/min, with further improvement as the dosage increased. In 2 ponies, 10 microg of dobutamine/kg/min caused cardiac arrhythmias. Dopexamine (1 and 5 microg/kg/min) increased CI, MAP, and IMBF in the nondependent muscle, and 10 microg/kg/min caused muscular tremor, sweating, and arrhythmias. SVR was reduced after infusion of dopamine, dobutamine, or dopexamine., Conclusion: During anesthesia of equids, an increase in Cl and MAP is necessary to improve IMBF in the dependent forelimb., Clinical Relevance: Of the agents investigated, dobutamine proved the most consistent in improving IMBF.

Objective: To document tolfenamic acid disposition variables, identify its major phase-1 metabolite and fragmentation pattern, and establish detection time in urine after single IV bolus administration to make recommendations on avoiding violative residues in racing camels., Animals: 7 healthy camels (6 males, 1 female), 8 to 11 years old and weighing from 300 to 480 kg., Procedure: Blood samples were collected at 0, 5, 10, 15, 30, 45, and 60 minutes and at 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 13, 14, 15, and 16 hours after IV administration of tolfenamic acid (2.0 mg/kg of body weight). Urine samples were collected daily for 14 days after drug administration. Serum tolfenamic acid concentration was measured; limit of quantification was 50 ng/ml. A metabolite of tolfenamic acid in urine was isolated and identified, and its major fragmentation pattern was verified. Screening for tolfenamic acid and its metabolite in urine was performed., Results: Mean +/- SEM tolfenamic acid elimination half-life was 5.76+/-0.26 hours. Total body clearance was 0.109+/-0.011 L/kg/h, and steady-state volume of distribution was 0.68+/-0.06 L/kg. Detection time for tolfenamic acid and its hydroxylated metabolite in urine after IV administration of a dose of 2.0 mg/kg was 5 and 7 days, respectively., Conclusions: Camels eliminate tolfenamic acid mainly via metabolism more slowly than do cattle. The extrapolated dose regimen from cattle to camels appears inappropriate. Veterinarians are advised not to use tolfenamic acid in camels for at least 8 days prior to racing.

Objective: To determine normal variation in, and effect of 2% pilocarpine hydrochloride on, intraocular pressure (IOP) and pupil size in female horses during a specified period., Animals: 10 female horses with normotensive eyes., Procedure: IOP and horizontal and vertical pupil size were measured on a single day between 8 AM and 8 PM at hours 0, 0.5, 1, 2, 4, 6, 8, 10, and 12. Measurements were repeated after single- dose application of 2% pilocarpine to both eyes. IOP and pupil size were measured at 8 AM and noon in a 5-day experiment of twice-daily application of 2% pilocarpine., Results: Variation in IOP and pupil size was not significant between 8 AM and 8 PM. Change in IOP or pupil size after a single dose of 2% pilocarpine also was not significant. In the multiple-dose experiment, the IOP at noon on the fifth day was significantly higher than the IOP in the morning on the first and second days. The IOP in the morning on the fifth day was significantly higher than the IOP in the morning and at noon on the first and second days. The IOP at noon on the fourth day was significantly higher than the morning IOP on the first and second days and at noon on the first day. The decrease in vertical pupil size was significant., Conclusions: Between 8 AM and 8 PM, variation in IOP and pupil size in normotensive eyes of horses is not significant. Two percent pilocarpine does not significantly change IOP between 8 AM and 8 PM in clinically normal horses after a single dose or multiple twice-daily applications. After multiple twice-daily applications, a trend toward an increase in IOP was seen, and the decrease in vertical pupil size was significant.

Objective: To compare pharmacokinetics of eltenac after first and last IV administrations (0.5 mg/kg), using a multiple dosing schedule., Animals: 6 adult mares., Procedure: Eltenac (50 mg/ml) was administered IV at a dosage of 0.5 mg/kg of body weight every 24 hours for days 0 through 4. On days 0 and 4, blood samples were collected before, then periodically for 8 hours after eltanac administration. Concentration of eltenac in plasma samples was determined by use of high-performance liquid chromatography., Results: On day 0, median area under the plasma eltenac concentration versus time curve (AUC) was 6.77 microg.h/ml (range, 5.61 to 8.08 microg.h/ml), median plasma clearance was 1.23 ml/min/kg (range, 1.03 to 1.40 ml/min/kg), and median steady-state volume of distribution was 191 ml/kg (range, 178 to 218 ml/kg). Median terminal half-life of eltenac was 2.36 hours (range, 2.30 to 2.98 hours). On day 4, median eltenac AUC was 6.70 microg.h/ml (range, 5.21 to 7.44 microg.h/ml), median plasma clearance was 1.23 ml/min/kg (range, 1.12 to 1.53 ml/min/kg), and median steady-state volume of distribution was 193 ml/kg (range, 172 to 205 ml/kg). Median terminal half-life of eltenac was 2.40 hours (range, 2.11 to 3.25 hours). Protein binding of eltenac, determined by ultrafiltration, was > 99% at a total plasma concentration of 36 microg/ml., Conclusion: Pharmacokinetic variables determined for each horse were not different between days 0 and 4., Clinical Relevance: Under conditions of this study, there was no clinically relevant accumulation of eltenac in equine plasma or alteration of pharmacokinetic variables after multiple IV dosing of 0.5 mg/kg of eltenac.

This paper describes the use of Bioglass synthetic bone graft particulate (PerioGlas/Consil) in the treatment of osseous periodontal defects, and in post-extraction sites to maintain the vertical height and width of the alveolar ridge. The material is easy to use, inhibits epithelial down-growth, and acts as a mechanical hemostatic agent. Radiographic follow up in 36 dogs and 5 cats demonstrated significant bone fill. In the osseous periodontal defect treatment group, clinical probing depths decreased significantly, and there was an apparent gain in attachment level.

Although neonatal altricial rodents are frequently used in experimental projects in which they must undergo survival surgical procedures, there are few published guidelines for anesthetizing them. Many of the drugs and methods that are commonly used to anesthetize newborn rodents provide inadequate anesthesia or are associated with problems, such as excessively high mortality. A two-part study was undertaken with the intention of identifying agents or methods that can be used to provide humane, safe, and effective anesthesia for neonatal rats. In part I, 1- to 3-day-old rat pups were anesthetized with methoxyflurane or one of several injectable agents, or by induction of hypothermia (immersion in ice water). Times to loss of the righting reflex, surgical anesthesia (indicated by loss of the pedal reflex and failure to respond to a skin incision), and recovery of the righting reflex were measured, and heart rate, respiratory rate, and oxygen saturation were monitored. Ketamine (100 mg/kg of body weight, i.p.), pentobarbital (30 to 40 mg/kg, i.p.), and fentanyl-droperidol combination (0.16 mg of fentanyl and 8.0 micrograms of droperidol/g, i.p.) proved unsafe (> 50% mortality) and/or ineffective at inducing short-term surgical anesthesia. In contrast, methoxyflurane and hypothermia were safe and effective. On the basis of subjective observations that they struggled and vocalized less, pups placed in protective latex sleeves prior to immersion in ice water appeared to be less distressed than pups immersed unprotected. In part II of the study, it was possible to safely maintain 1- to 3-day-old pups at a surgical plane of anesthesia for 30 min with either methoxyflurane or hypothermia. Supplementation with pentobarbital (20 mg/kg, i.p.) offered no advantages but significantly prolonged time to recovery. Surviving pups in both studies grew at similar rates during the month after testing. It was concluded that methoxyflurane or hypothermia are good choices for short- or long-term anesthesia of neonatal rats, and that use of a protective sleeve appears to reduce distress associated with induction of profound hypothermia.

Recombinant human factor IX (rFIX) has been expressed in transduced cultured cell systems since 1985. Because there has been limited in vivo testing of rFIX in hemophilia B subjects, this study was undertaken using the severe hemophilia B canines of the Chapel Hill strain. Three groups of hemophilic dogs received either 50, 100, or 200 IU/kg of rFIX. As a control, a fourth group of hemophilic dogs received 50 IU/kg of a high purity, plasma-derived human FIX (pdFIX). The coagulant and hemostatic effects of rFIX and pdFIX were similar with all comparative dosing regimens. Based on activity data, the elimination half-life of rFIX was 18.9 +/- 2.3 hours and pdFIX was 17.9 +/- 2.1 hours. A prophylactic regimen administering rFIX daily resulted in a continuous therapeutic level of plasma FIX and was accompanied by a two-fold increase in recovery levels by day 5, compared to that observed with administration of a single bolus. The mechanisms of the high to complete recovery of FIX with the prophylactic regimen could depend not only on the degree of saturation of the vascular endothelial binding sites but also on the altered dynamics of the balance of FIX distribution between the intravascular and extravascular compartments. The pharmacokinetic (PK) parameters for rFIX and pdFIX were similar. However, the relative PK values for V1 and V5s of both products on day 5 differed greatly from day 1 and may reflect the changing equilibrium of FIX between compartments with elevated levels of plasma FIX. Neutralizing antihuman FIX antibodies resulting from human FIX antigen being administered to FIX deficient dogs were observed beginning at 14 days. The antigenicity of rFIX and pdFIX appeared to be comparable. Despite the very different procedures used for production of rFIX and pdFIX products, in vivo testing in hemophilia B dogs showed the functional behavior of these products is similar; they are highly effective for replacement therapy and for prophylaxis.

Tilmicosin(TM), a macrolide antibiotic and active ingredient in formulated Micotil 300 (Eli Lilly and Co., Indianapolis, IN, USA), is the active ingredient in a formulated animal product used for the treatment of respiratory tract infections in cattle. Owing to the concern of governmental regulatory agencies over the possibility of an accidental injection of the antibiotic to a livestock handler, the cardiovascular effects of sub lethal doses of TM were evaluated in conscious mixed-breed dogs. Left ventricular function, systemic arterial blood pressure, and heart rate (HR) responses to TM alone and in combination with propranolol(P) or dobutamine HCl(DOB) were evaluated. Dogs were instrumented with indwelling micromanometers implanted in the left ventricular chamber and in the thoracic aorta. Cardiovascular variables were recorded, and the peak value of the first derivative of left ventricular pressure (dp/dt(max)) was used as an index of left ventricular inotropic state. Six treatments were randomly assigned to each of the six dogs using a Latin square design. The six treatments were vehicle, TM alone (2.5 mg/kg of body weight), TM immediately followed by P, and TM immediately followed by 1 of 3 dosages of DOB infused for approximately 45 min. Additionally, doses of TM alone (0.25, 1.0, 2.5, and 5.0 mg/kg) were administered to complete a dose-response curve. TM caused dose dependent decreases in (dp/dt(max)) and aortic pulse pressure. HR increased dose-dependently. Left ventricular end-diastolic pressure increased at the 2.5 and 5.0 mg/kg dosages. Left ventricular systolic pressure was reduced dose-dependently at the 2.5 and 5.0 mg/kg dosages. Treatment with P exacerbated the negative inotropic effect and the decrease in left ventricular systolic pressure, but did not attenuate the tachycardia associated with TM treatment. DOB attenuated the changes in ventricular inotropic state in a dose-dependent manner. DOB infusion also restored left ventricular systolic pressure at dosages of 3 or 10 micrograms/min/kg. Our data indicate that toxic doses of TM may have a negative inotropic effect in conscious dogs. HR increased in a dose-dependent manner and was not the result of beta 1-receptor stimulation. DOB reversed some, but not all, of the effects caused by TM administration.

The efficacy of a phyto-aromatic gel (Canidor) was evaluated, in vitro against Psoroptes cuniculi and in vivo against P cuniculi and Otodects cynotis, in experimentally and naturally infested rabbits and domestic carnivores respectively. At a 1/1 dilution the gel was 100 per cent active in vitro against P cuniculi after less than six hours of contact. In experimentally infested rabbits the gel was administered daily during two periods of five consecutive days, six days apart. A clinical cure was achieved in all the animals, but two harboured a few eggs and mites at the end of the trial. In dogs and cats the active formulation was given for two periods of four consecutive days, seven days apart. Clinical and parasitological examinations 10 and 30 days after initiating the treatment regiment revealed an excellent acaricidal effect.

Adverse reactions to various trimethoprim-sulphonamide (T-S) combinations were studied retrospectively in dogs and cats referred to the Utrecht University Department of Clinical Sciences of Companion Animals during the period 1985-1994. Dermatological and systemic reactions were observed in 19 dogs and 2 cats. Specific histological reaction patterns were seen in 3 dogs with toxic epidermal necrolysis, in 1 dog and 1 cat with erythema multiforme, and in 1 dog with pemphigus foliaceus. Diagnostic criteria used in humans proved to be reliable in dogs and cats as well. Adverse reactions were observed within 7-14 days after administration and were most often due to sulphadiazine (76%) and sulphatroxazole (14%). The incidence of adverse reactions to T-S was 0.25%.

The clinical efficacy and safety of enalapril were evaluated in dogs with moderate or severe heart failure. This study was conducted at 19 centers and included 211 client-owned dogs with heart failure caused by mitral regurgitation (MR) due to acquired valvular disease or dilated cardiomyopathy (DCM). Dogs of various breeds, ages, and weights were included in the study. Replicates of 2 dogs each were formed, using separate allocation schedules for dogs with MR or DCM. One dog within each replicate received placebo tablets (vehicle tablets without enalapril) PO sid or bid, and the other dog received enalapril tablets at approximately 0.5 mg/kg sid or bid, based on individual need. In addition to the experimental drug, all dogs, except 1 in the placebo group, received furosemide; 73.3% of the dogs in the placebo group and 78.3% of those in the enalapril group received digoxin. Doses of enalapril or placebo were administered for approximately 28 days. In the placebo group, 68.6% of the dogs completed the study compared with 84.9% in the enalapril group; the difference between groups was significant (P < .01). Significantly (P < .01) more dogs in the placebo group compared with the enalapril group died or were removed from the study because of progression of heart failure. On day 28, all 14 clinical variables measured improved significantly (P < .01) in the enalapril group compared with the placebo group. Five dogs (3 from the placebo group and 2 from the enalapril group) had to be removed from the study as a result of azotemia.

The efficacy of enalapril maleate in dogs with naturally acquired class III or class IV heart failure was evaluated in a multicenter study. Fifty-eight dogs with dilated cardiomyopathy (35 dogs), mitral regurgitation (22 dogs), or aortic regurgitation (1 dog) receiving conventional therapy for heart failure (furosemide with or without digoxin) were included in a randomized double-blind study. Thirty-one dogs received enalapril tablets PO at approximately 0.5 mg/kg body weight bid, and 27 dogs received placebo tablets PO bid. Physical, electrocardiographic, hemodynamic, echocardiographic, radiographic, and clinical examinations were performed on each dog before treatment and at the end of the approximately 21-day study. After treatment on day 0, the enalapril-treated dogs had significantly (P < .05) lower heart rate, mean systemic arterial blood pressure, and mean pulmonary arterial blood pressure than the placebo-treated dogs. Pulmonary capillary wedge pressure was marginally decreased (P = .0567) in the enalapril-treated dogs. When compared with those in the placebo-treated dogs, scores for pulmonary edema were significantly (P < .05) decreased on day 2 in the enalapril-treated dogs. At the end of the study, enalapril-treated dogs had significantly (P < .05) greater decreases in class of heart failure, pulmonary edema score, and mobility score relative to baseline, and had significantly (P < .05) better overall evaluation scores when compared with the placebo-treated dogs. This study shows the beneficial hemodynamic and clinical effects of adding enalapril to conventional therapy for dogs with heart failure.

Seven commonly used, topical antifungal products (i.e., lime sulfur, chlorhexidine, captan, povidone-iodine, sodium hypochlorite, and enilconazole solutions, and ketoconazole shampoo) were evaluated for their antifungal activity on Microsporum canis-infected hairs from dogs and cats in an in vitro study. Hairs were soaked or shampooed in each product for five minutes twice a week for four weeks. Of the seven products used in this study, lime sulfur and enilconazole solutions were superior in inhibiting fungal growth; no growth occurred on fungal cultures after two treatments with either product. Chlorhexidine and povidone iodine solutions were effective after four treatments, and sodium hypochlorite solution and ketoconazole shampoo inhibited fungal growth after eight treatments. Captan did not inhibit fungal growth during the test period.

The hemodynamic effects of interpleural (IP) bupivacaine were studied in six halothane-anesthetized dogs. On four separate occasions, each dog received IP saline (S), or bupivacaine at a low dosage of 1.5 mg/kg (L), high dosage of 3.0 mg/kg (H), or high dosage of 3.0 mg/kg with epinephrine 5 micrograms/mL (HE). Heart rate, systolic and mean arterial pressures, and base excess were significantly lower in the H dosage group than in the other treatment groups. Cardiac output, expressed as a percentage of change from baseline, was significantly higher in the L group than in the H and S groups. Pulmonary arterial pressure and respiratory rate were significantly higher in the HE group than in the other three groups. Mean plasma concentrations of bupivacaine peaked between 5 and 15 minutes after IP injection. Maximum plasma concentrations in individual dogs were variable; however, mean maximum plasma concentrations in the H and HE groups were not significantly different. Clinically significant hypotension occurred in one dog in the H group and in one dog in the HE group. No pulmonary complications were detected.

This study provides baseline information on the potential use of propofol as a general anesthetic for horses. Using a Latin square design, propofol (2, 4, and 8 mg/kg) was administered intravenously on three separate occasions to six mature horses. Information about anesthetic induction, duration, and recovery was recorded along with results of rectal temperature, heart rate, respiratory rate, pHa, PaCO2 and PaO2. Statistical analysis included a mixed model analysis of variance, a general linear model analysis and least square means test for post hoc comparisons. A P < .05 was considered significant. The quality of induction of anesthesia varied from poor to good. Two horses were not recumbent following the lowest dose of propofol. Brief paddling limb movements occurred occasionally and unpredictably after recumbency induced by all three doses. During recovery, horses were uniformly calm and coordinated in their moves to stand. Duration of recumbency (minutes) was dose related; 15.05 +/- 1.58 (mean +/- SD) following 2 mg/kg, 31.06 +/- 5.56 following 4 mg/kg, and 47.85 +/- 13.63 following 8 mg/kg. During recumbency at all doses, heart rate significantly increased from a predrug value of 40 +/- 6 beats per minute. Substantial respiratory depression, characterized by a significant decrease in respiratory rate (from 11.7 +/- 2.9 to 3.7 +/- 1.6 breaths per minute) and increased PaCO2 (from 44.5 +/- 2.5 to 52.7 +/- 8.0 mm Hg) was seen only after 8 mg/kg. A significant decrease in PaO2 was observed throughout the recumbency induced by 8 mg/kg, and also at 3 and 5 minutes following induction of anesthesia with 4 mg/kg propofol.(ABSTRACT TRUNCATED AT 250 WORDS)

The availability of safe and effective drugs to treat and control poultry diseases and to enhance the efficiency of poultry production depends on the rate at which new drugs are approved by the Food and Drug Administration. This paper briefly describes the components of the regulatory approval process for a new animal drug for use in food-producing animals, with specific reference to some problems encountered in the approval process for poultry drugs.

Guidelines have been designed to assist in the planning, operation and interpretation of studies for the assessment of the efficacy of drugs against helminth parasites of dogs and cats. The advantages, disadvantages and application of critical and controlled tests are presented. Information is also provided on the selection of animals, housing, feeding, dose-titration, confirmatory and clinical trials, record keeping and necropsy procedures. These guidelines should assist both investigators and registration authorities involved in the evaluation of anthelmintics to employ comparable and standard procedures and will have the added benefit of minimising the numbers of animals needed for such tests.

The immunogenic potency of an experimental vaccine against rotavirus infection of cattle was studied under production conditions. Cows with calves were vaccinated in the second period of pregnancy once, twice and three times. The study showed the schedule of immunization of pregnant cows including three vaccinations at 50-40, 30-20, and 15-10 days before delivery to be technological, providing a high protective effect in newborn calves.

Twenty-nine free-ranging Norwegian cattle were captured with xylazine (n = 20) or medetomidine (n = 9) using a tranquilizing gun, and the time from darting to recumbency (induction time) was recorded. Twenty-eight animals were given atipamezole IV 15-100 min after darting, and the effects of the antagonist were evaluated. Blood samples (n = 19) for haematology and serum chemistry were collected within 10 min after immobilization was induced. Xylazine (0.55 +/- 0.18 mg/kg; mean +/- SD; n = 18) or medetomidine-HCl (0.039 +/- 0.10 mg/kg; n = 8) induced complete immobilization after a single darting with sternal or lateral recumbency, the induction times being 9.6 +/- 3.8 and 12.0 +/- 6.8 min, respectively. No difference in the clinical effects of the two drugs was observed. Rapid reversal was achieved with 0.057 +/- 0.017 and 0.077 +/- 0.019 mg/kg of atipamezole-HCl in xylazine- and medetomidine-treated animals, respectively. All the animals stood within 2 min after IV administration of the antagonist. Seven animals showed signs of excitement shortly after reversal, but these side-effects were of brief duration. Heavy resedation with relapse into recumbency was seen 3-4 h after reversal in two cows captured with xylazine, while moderate resedation was observed in two medetomidine-treated animals 2 h after reversal. Except for the plasma glucose concentration, which was elevated in both xylazine- and medetomidine-treated animals, the mean values of the haematological and plasma chemical parameters were within the reference ranges established for Norwegian cattle.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of sulbactam, a beta-lactamase inhibitor, in combination with ampicillin, was evaluated for treatment of experimentally induced pneumonia caused by beta-lactam-resistant Klebsiella pneumoniae. Infection was experimentally induced in 18 healthy weanling foals that were randomly allocated to 3 treatment groups: sulbactam plus ampicillin (S/A, 3.3 and 6.6 mg/kg of body weight, respectively), ampicillin (6.6 mg/kg), or vehicle only. Foals were treated daily for 7 days; the observer was unaware of treatment status. Compared with ampicillin and vehicle, treatment with S/A resulted in a statistically significant (P less than 0.05) decrease in severity of pneumonia, with regard to bronchoalveolar lavage cytologic findings (decreased total cell and neutrophil numbers, and increased lymphocyte numbers) and extent of macroscopic lesions in lung tissue of the noninoculated regions. Marked trends toward improvement of S/A-treated foals were observed for quantitative results of bacteriologic culture of bronchoalveolar lavage fluid samples (P less than 0.07), macroscopic pathologic features of the whole lung (P less than 0.1), and histopathologic variables (P less than 0.07), compared with ampicillin- and vehicle-treated foals. Treatment effects were not observed for radiographic, hematologic, and blood gas abnormalities that resulted from infection. In conclusion, the combination of sulbactam plus ampicillin was found to have synergistic effects in vivo, to reduce the extent and severity of experimentally induced gram-negative lung infection in foals.

Danofloxacin, a novel fluoroquinolone antimicrobial drug was evaluated in the treatment of acute bacterial pneumonia in recently housed beef cattle of approximately 300 kg liveweight. The clinical responses of 67 pneumonic cattle treated with danofloxacin were compared with those of 65 cattle treated with oxytetracycline, both treatments being given by intramuscular injection for either three or five days, depending on clinical response. Both treatments resulted in a rapid fall in group mean rectal temperature and improved the clinical condition of the majority of cases. However, in comparison with oxytetracycline, danofloxacin therapy was characterised by significantly fewer treatment days, a higher response rate, significantly better reduction of pyrexia and fewer cattle requiring re-treatment.