Evaluation of the distribution of enrofloxacin by circulating leukocytes to sites of inflammation in dogs.

OBJECTIVE: To determine the effect of WBC accumulation on the concentration of enrofloxacin in inflamed tissues in dogs. ANIMALS: 6 adult Bloodhounds. PROCEDURES: Dogs were instrumented bilaterally with tissue chambers. Peripheral WBCs collected from each dog were exposed in vitro to radiolabeled enrofloxacin ((14)C-ENR). Inflammation was induced with carrageenan in 1 chamber. Ten hours later, treated cells were administered IV to each dog such that (14)C-ENR was delivered at a mean +/- SD dosage of 212 +/- 43 microg. Samples of extracellular fluid from inflammation and control chambers and circulating blood were then collected before (baseline) and for 24 hours after WBCs were administered. Samples were centrifuged to separate WBCs from plasma (blood) or chamber fluid. Radiolabeled enrofloxacin was scintigraphically detected and pharmacokinetically analyzed. Comparisons were made between extra- and intracellular chamber fluids by use of a Student paired t test. RESULTS: (14)C-ENR was not detectable in plasma, peripheral WBCs, control chambers, or baseline samples from inflammation chambers. However, (14)C-ENR was detected in extra- cellular fluid from inflammation chambers (mean +/- SD maximum concentration, 2.3 +/- 0.5 ng/mL) and WBCs (maximum concentration, 7.7 +/- 1.9 ng/mL). Mean disappearance half-life of (14)C-ENR from extracellular fluid and WBCs from inflammation chambers was 26 +/- 10 hours and 17 +/- 6 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: WBCs were responsible for the transport and release of (14)C-ENR at sites of inflammation. Accumulation of drug by WBCs might increase the concentration of drug at the site of infection, thus facilitating therapeutic success.

Efficacy of fipronil in the treatment of feline cheyletiellosis.

The purpose of the present study was to confirm the efficacy of 10% (w/v) fipronil spot-on (Frontline spot-on for cats) in the treatment of feline cheyletiellosis under field conditions. A total of 16 cats of different breeds, sexes, 4 months to 14 years of age and weighing 0.5-6 kg were treated with a single topical application of 10% (w/v) fipronil spot-on according to label directions. The animals were naturally infested with Cheyletiella mites and housed in their normal environment throughout the study. Animals were selected based on clinical signs and infestation was confirmed by demonstration of mites. Mite counts and a clinical assessment of mite infestations (i.e. skin lesions and/or scales) were performed on days 0 and approximately days 14 and 28. Individual counts on day 0 ranged from 1 to 40 mites on individual animals. No mites were detected on cats treated with 10% (w/v) fipronil spot-on (Frontline spot-on for cats) at both post-treatment evaluations. Typical skin lesions and/or scales were present in all animals pre-treatment. In 56% of the cats, the lesions resolved within 14 days after treatment. At the final assessment, 75% cats were free of lesions. Two cats that still had clinical signs on day 28 were suspected of having allergic reactions to food or environmental allergens. The lesions on the remaining two cats could not be related to a specific cause. The efficacy of fipronil in elimination of mites was 100% on each occasion when compared to the pre-treatment count. The results of this study demonstrated that fipronil in a topical formulation is highly effective (100%) for the elimination of an existing Cheyletiella mite infestation under field conditions following a single topical application in cats.

Efficacy of fipronil/(S)-methoprene combination spot-on for dogs against shed eggs, emerging and existing adult cat fleas (Ctenocephalides felis, Bouché).

The inhibitory activities of fipronil (10% (w/v) solution), (S)-methoprene (9% (w/v) solution), and fipronil/(S)-methoprene (10 and 9% (w/v) solution, respectively) combination against eggs and emerging adult cat fleas (Ctenocephalides felis) and adulticidal activity were tested on experimentally infested dogs. Thirty-two Beagle dogs were selected for this study and eight replicates of four animals were formed based on body weight within sex. One dog in each replicate was randomly allocated to treatment with: (1) untreated control; (2) fipronil 10% (w/v) solution, (3) (S)-methoprene 9% (w/v) solution, and (4) fipronil 10% (w/v) and (S)-methoprene 9% (w/v) combination solution. Treatments were applied once topically on Day 0 at the rate of 0.067 ml/kg. On Days -12, -1, 21, and weekly to Day 84 each dog was infested with approximately 200 fleas and comb counted approximately 24h later, or 2 days (our 48 h) after in the case of Day -1 infestation. On Days -11, 1, 22, and weekly to Day 85 each dog was again infested with approximately 200 fleas. Flea eggs were collected over approximately 24 h beginning 3 days after infestation. Fleas were combed off of the dogs and counted at the end of the egg collection period (approximately 96 h count). One aliquot of up to about 100 eggs, if available, from each animal at each infestation time was incubated for approximately 72 h to determine larval hatch and the other for 35 days to determine the number of adults that developed. The 10% (w/v) fipronil spot-on provided excellent control (>95%) of adult fleas on dogs for 5 weeks. Similarly, the combination spot-on of 10% (w/v) fipronil and 9% (w/v) (S)-methoprene provided excellent control of adult fleas, i.e., >95% for 5 weeks. From week 6 post-treatment onward, the relatively low inhibition of adult flea emergence substantiated the lack of significant ovicidal/larvicidal activity in the fipronil (10%, w/v) treatment group. However, the combination product provided excellent (>90%) ovicidal activity for 8 weeks and high (91.4%) inhibition of adult flea emergence for 12 weeks. In addition, a synergistic effect of the two compounds in combination was demonstrated with fipronil enhancing the ovicidal and inhibition of adult flea emergence activity of (S)-methoprene against cat flea eggs. When all stages of the life cycle of the cat flea are considered, the combination spot-on product provided a high level of total flea control yielding a curative effect against adult fleas and inhibition of flea development stages with little to no potential reinfestation pressure on the animal or in the environment for 12 weeks.

Hyperactivity and alopecia associated with ingestion of valproic acid in a cat.

A 1-year-old castrated male cat was evaluated because of alopecia of approximately 4 to 5 months' duration as well as hyperactive behavior. It was later determined that the cat was ingesting valproic acid by eating food to which it had been added for daily administration to a child in the household who had cerebral palsy. The clinical signs slowly resolved after the source of valproic acid was removed. This emphasizes the sensitivity of cats to drugs that are commonly used in humans. It was not determined whether the clinical signs that developed in this cat were caused by an adverse reaction or from toxicosis as a result of prolonged hepatic elimination of valproic acid, which requires glucuronide metabolism for disposition. However, the cat recovered completely following removal of the drug and prevention of further exposure. This report emphasizes the importance of obtaining a careful and complete history from the owner regarding an animal and its environment. In the cat of this report, the owner had not considered the impact of the presence of the drug in the child's food.

Time course of enrofloxacin and its active metabolite in peripheral leukocytes of dogs.

The accumulation of fluoroquinolones in peripheral leukocytes is well established for several members of this family of drugs. This study documented accumulation of enrofloxacin and its active metabolite, ciprofloxacin, in canine peripheral leukocytes after oral administration at 7.5, 10, or 20 mg/kg, doses that are within the currently approved label of Baytril (Bayer Corporation Animal Health, Shawnee Mission, KS) in the United States. Accumulation index, as defined by C(max) in white blood cells (WBCs) divided by C(max) in plasma at the same time points, ranged from 47-fold to 63-fold for enrofloxacin and 28- to 35-fold for ciprofloxacin. Time course of both enrofloxacin and ciprofloxacin in WBCs paralleled the time course in plasma. Disappearance half-life of ciprofloxacin from WBCs was significantly (P = .001) longer than was enrofloxacin (P= .015) for all doses studied. The accumulation of enrofloxacin in peripheral leukocytes may contribute to the antimicrobial efficacy of this compound.

Tissue concentrations of enrofloxacin and ciprofloxacin in anesthetized dogs following single intravenous administration.

Concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were detected in tissues following single intravenous administration of 20 mg/kg to four anesthetized dogs. Two hours after treatment, serum samples were collected, animals were euthanized, and tissues were collected from each dog. Solid tissues were homogenized, and both enrofloxacin and ciprofloxacin were detected using high-performance liquid chromatography. Enrofloxacin was detected in all tissues examined; the highest concentrations were found in the gall bladder, urine, bile, stomach, and liver. Concentrations in the cerebral cortex, cerebrospinal fluid, skin, and prostate were 5.7, 5.3, 9.2, and 23.5 microg/ml, respectively. Tissues for which the concentration of enrofloxacin was 4 microg/ml or lower included the trachea, articular cartilage, aqueous humor, fat, and tendon. An inhibitory quotient of 8 or more was achieved for enrofloxacin in the majority of tissues studied. Ciprofloxacin was detected in 29 of 40 tissues examined.

Pharmacokinetics of the bovine formulation of enrofloxacin (Baytril 100) in horses.

Following approval of a concentrated injectable formulation of enrofloxacin for cattle (Baytril 100 Injectable, Bayer Corp. Agricultural Division, Shawnee Mission, KS), equine practitioners have started administering this preparation both parenterally and orally to horses, despite the lack of pharmacokinetic data in this species. Six healthy horses received enrofloxacin at 7.5 mg/kg both orally and intravenously, with the sequence being randomly assigned and at least 1 week of washout allowed between administrations. Blood samples were collected from each horse at various intervals after drug administration to study the pharmacokinetic profile of this product. As concentration-dependent antimicrobials, fluorinated quinolones such as enrofloxacin are most efficacious when the inhibitory quotient is at least 8. In this study, based on inhibitory quotients between 8 and 10, the bovine injectable formulation of enrofloxacin administered to horses intravenously or orally once daily at 7.5 mg/kg may be effective against susceptible organisms whose minimum inhibitory concentration for 90% of the isolates is lower than 0.5 microg/ml.