Evaluation of the efficacy and safety of a novel formulation of metaflumizone in cats naturally infested with fleas in Europe

The efficacy and safety of a novel spot-on formulation of metaflumizone (ProMeris for Cats, Fort Dodge Animal Health, Overland Park, KS) was assessed in cats naturally infested with fleas in a multiregional, clinical field study. Sixteen veterinary clinics in Germany and eight clinics in France enrolled patients to the study. A total of 173 cats with flea infestation qualified as primary patients and were randomly allocated to one of the two treatments in a ratio of approximately 2:1 for metaflumizone (minimum dosage of 40mg/kg) or fipronil (at the recommended label rate). Clinical examinations and baseline parasite counts were performed on Day 0 prior to treatment. Flea counts and safety evaluations were repeated at approximately 2-week intervals for 8 weeks. Both treatments resulted in consistent reductions (>84%) in flea numbers throughout the study, but metaflumizone resulted in numerically higher reductions on most count days. Within groups the flea reduction was highly significant (p<0.0001) compared to baseline at all observation periods. The efficacy of metaflumizone against fleas compared to baseline was 91.0%, 89.4%, 90.8% and 90.7% at Day 14, 28, 42 and 56, respectively. The corresponding efficacies for fipronil were 91.7%, 86.9%, 84.6% and 87.7%. Metaflumizone was highly effective in controlling existing infestations of fleas on cats and was effective against reinfestation for at least 56 days. Metaflumizone showed a good tolerance profile in cats.     

Efficacy of selamectin in the treatment and control of clinical signs of flea allergy dermatitis in dogs and cats experimentally infested with fleas

OBJECTIVE: To determine whether treatment with selamectin would reduce clinical signs of flea allergy dermatitis (FAD) in dogs and cats housed in flea-infested environments. DESIGN: Randomized controlled trial. ANIMALS: 22 dogs and 17 cats confirmed to have FAD. PROCEDURE: Animals were housed in carpeted pens capable of supporting the flea life cycle and infested with 100 fleas (Ctenocephalides felis) on days -13 and -2 and on alternate weeks with 10 to 20 fleas. On day 0, 11 dogs and 8 cats were treated with selamectin (6 mg/kg [2.7 mg/lb]). Dogs were retreated on day 30; cats were retreated on days 30 and 60. All animals were examined periodically for clinical signs of FAD. Flea counts were conducted at weekly intervals. RESULTS: Throughout the study, geometric mean flea counts exceeded 100 for control animals and were < or = 11 for selamectin-treated animals. Selamectin-treated cats had significant improvements in the severity of miliary lesions and scaling or crusting on days 42 and 84, compared with conditions on day -8, and in severity of excoriation on day 42. In contrast, control cats did not have any significant improvements in any of the clinical signs of FAD. Selamectin-treated dogs had significant improvements in all clinical signs on days 28 and 61, but in control dogs, severity of clinical signs of FAD was not significantly different from baseline severity at any time. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that topical administration of selamectin, even without the use of supplementary environmental control measures and with minimal therapeutic intervention, can reduce the severity of clinical signs of FAD in dogs and cats.     

灭蚤项圈对犬、猫蚤的临床试验

采用自身对照试验，以自然感染栉首蚤（Ctenocephalides sp．）的犬与猫为试验动物，验证常熟市金牧药业有限公司生产的灭蚤项圈（犬用、猫用）对蚤的杀灭与防治效果。结果表明：在整个试验期间，所有参与试验的犬、猫均未出现任何不良反应，犬、猫在挂项圈（即用药）后第14～60天，杀虫率分别在97．3％～98．4％与96．6％～98．0％之间，杀虫效果极显著（P〈o．01）。证明灭蚤项圈（犬用、猫用）对犬、猫安全可靠，能长期杀灭犬、猫蚤类。     

Control of fleas on naturally infested dogs and cats and in private residences with topical spot applications of fipronil or imidacloprid

Thirty-four flea-infested dogs and cats residing in 20 homes in Tampa, FL were randomly placed into 1 of 2 treatment groups during the summer of 1997. Pets were treated topically with either 10.0%w/v imidacloprid or 10%w/v fipronil spot-on on day 0, then once for every 28-30 days for 90 days. Flea populations were assessed in the environment using an intermittent-light trap, while pet flea burdens were assessed using visual area counts. A single application of imidacloprid was 95.3 and 97.4% effective in reducing flea populations on pets at 7 and 28 days, respectively. A single application of fipronil was 97.5 and 97.0% effective in reducing flea populations on pets at the same time points. Following 3 monthly applications of either imidacloprid or fipronil, flea burdens on pets were reduced by 99.5 and 96.5%, respectively. In addition, flea numbers in the in-home environment were reduced by 99. 0 and 98.6% in homes, where pets were treated with imidacloprid or fipronil, respectively.     

Evaluation of the efficacy and safety of a novel formulation of metaflumizone plus amitraz in dogs naturally infested with fleas and ticks in Europe

The efficacy and safety of a novel spot-on formulation of metaflumizone plus amitraz (ProMeris/ProMeris Duo for Dogs, Fort Dodge Animal Health, Overland Park, KS) was assessed in dogs naturally infested with ticks and/or fleas in a multiregional, clinical field study. Nineteen veterinary clinics in Germany and 11 clinics in France enrolled patients to the study. One hundred eighty one dogs with tick infestation and 170 dogs with flea infestation (plus three dogs harboring both ticks and fleas) qualified as primary patients and were randomly allocated to one of two treatments in a ratio of approximately 2:1 for metaflumizone plus amitraz (minimum dosage of 20 plus 20mg/kg) or fipronil (at the recommended label rate). Clinical examinations and baseline parasite counts were performed on Day 0 prior to treatment. Tick and/or flea counts and safety evaluations were repeated at intervals of about 2 weeks for 8 weeks. Both products resulted in consistent reductions in tick numbers (>81%) throughout the study, with metaflumizone plus amitraz giving consistently higher reductions in tick numbers. The efficacy against tick count compared with Day 0 was 97.6%, 93.5%, 89% and 94% at Day 14, 28, 42 and 56, respectively, for metaflumizone plus amitraz. The corresponding efficacies for fipronil were 86.3%, 81.1%, 84.8% and 86.1%. Within groups, the tick reduction was highly significant (P<0.0001) compared to baseline at all observation periods. Both treatments resulted in consistent (>89%) and highly significant (P<0.0001) reductions in flea numbers relative to the baseline counts throughout the study, although fipronil resulted in numerically higher reductions on each count day. The efficacy against fleas compared to baseline was 91.8%, 88.7%, 91.5% and 92.0% at Day 14, 28, 42 and 56, respectively, for metaflumizone plus amitraz. The corresponding efficacies for fipronil were 98.2%, 96.3%, 95.9% and 96.7%. Metaflumizone plus amitraz was highly effective in controlling existing infestations of fleas and ticks on dogs and was effective against reinfestation for at least 56 days. Metaflumizone plus amitraz showed a good tolerance profile in dogs.     

Pharmacokinetics of an injectable long-acting formulation of doxycycline hyclate in dogs

Based on its PK/PD ratios, doxycycline hyclate (DOX-h), a time-dependant antibacterial, is ideally expected to achieve both sustained plasma drug concentrations at or slightly above the MIC level for as long as possible between dosing intervals. Pursuing this end, a poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its SC injection to dogs (≤ 0.3 mL per injection site), and results compared with the oral (PO) and IV pharmacokinetics of DOX-h, prepared as tablet or as freshly made solution. A crossover (4 x 4 x 4) study design was employed with 12 Mongrel dogs, with washout periods of 21 days, and at dose of 10 mg/kg in all cases. DOX-h-LA showed the greatest values for bioavailability (199.48%); maximum serum concentration (Cmax) value was 2.8 ± 0.3 with a time to reach Cmax (Tmax) of 2.11 ± 0.12 h and an elimination half-life of 133.61 ± 6.32 h. Considering minimum effective serum concentration of 0.5 μg/mL, a dose-interval of at least 1 week h can be achieved for DOX-h-LA, and only 48 h and 24 h after the IV or PO administration of DOX-h as a solution or as tablets, respectively. A non-painful small bulge, apparently non-inflammatory could be distinguished at injection sites. These lumps dissipated completely in 30 days in all cases.     

Carprofen as an analgesic for postoperative pain in cats: Dose titration and assessment of efficacy in comparison to pethidine hydrochloride

The aim of this study was to titrate the optimal dose of carprofen for single dose usage, for alleviating postoperative pain, under a double-blind and randomised protocol, using both negative and positive controls. Renal tolerance was assessed by screening plasma urea and creatinine. Pre- and postoperative assessment of pain and sedation was made using a dynamic and interactive visual analogue scoring system in 60 cats undergoing ovariohysterectomy. The cats were randomly assigned to one of six groups: (1) carprofen at 1-0 mg/kg subcutaneously (sc); (2) carprofen at 2-0 mg/kg sc; (3) carprofen at 4-0 mg/kg sc; (4) pethidine at 5-0 mg/kg intramuscularly (im), (5) pethidine at 10-0 mg/kg im; and (6) no analgesics (injection of saline). All injections were given postoperatively on tracheal extuba-tion and administered in a double-blind manner. Assessments were made up to 20 hours post extubation. Prior to induction and at 20 hours post extubation, blood samples were taken for laboratory analysis of the urea and creatinine content to check for any adverse effect on renal function. Cats given pethidine did not appear more sedated than the groups receiving carprofen or saline. Cats receiving carprofen were in less pain postoperatively overall, with 4-0 mg/kg being the most effective dose rate (significantly better than the other doses of carprofen at four and eight hours post extubation). The highest dose of pethidine provided significantly better analgesia than the highest dose of carprofen up to two hours post extubation, but from two to 20 hours post extubation carprofen at 4-0 mg/kg provided significantly better analgesia than the pethidine. None of the analgesic regimens appeared to affect renal function adversely, as measured by urea and creatinine levels.     

Prevalence of fleas on dogs and cats in an area of central London

An account is given of the prevalence of fleas obtained at post-mortem examination from dogs and cats in the Camden Town area of central London during the period 1972–1976. From a total of 193 dogs, fleas were collected from 20 2%. The following species were represented: Ctenocephalides felis felis, Ctenocephalides canis and Orchopeas howardi. Of a total of 316 cats, 56% harboured fleas, all of which were found to be Ctenocephalides felis felis. The advantages of using cadavers rather than live cats and dogs for studies of this kind are noted and comparisons are made with the findings of other authors. The public health importance of the cat and dog flea in relation to human dermatitis is discussed.     

Pharmacokinetics of an injectable sustained-release formulation of morphine for use in dogs

This study investigated the pharmacokinetics of morphine sulphate in an injectable chitosan-based gel. Gels were made from a combination of N-O-carboxymethylchitosan (NOCC) and chitosan and were easily injectable via a 22 gauge needle and appeared stable during long-term storage. Groups of six beagles were injected subcutaneously (s.c.) with 1.2 mg/kg morphine sulphate, either in sterile saline or in sterilized gels, and serial blood samples were withdrawn via a jugular catheter and later analysed for morphine concentrations using radioimmunoassay. Data were analysed according to non-compartmental pharmacokinetics. NOCC-based gels resulted in significantly lower serum morphine concentrations at 10 and 30 min following injection but significantly higher concentrations at all points from 120 to 480 min post-injection. Dogs receiving morphine gel exhibited equivalent or lesser variability in serum morphine concentrations than dogs receiving conventional morphine sulphate. Pharmacokinetic analysis revealed that morphine release from the gel matrix was significantly prolonged but fully bioavailable. There were no significant differences in either distribution ( V _d) or terminal elimination ( t _1/2). Dogs experienced no adverse effects other than those normally associated with morphine administration at the time of injection but all dogs receiving the gel presented with an undefined stiffness the next day that resolved spontaneously within 48 h. We conclude that carboxymethylchitosan-based gels hold considerable promise for the development of injectable sustained-release formulations of opioid analgesics.     

P‐13 Dermatophytosis in domestic cats: treatment with lufenuron

Preliminary studies showed that lufenuron inhibits chitin synthesis, a dermatophyte cell wall constituent, and may be effective in the treatment of dermatophytosis. Our purpose was to evaluate the efficacy of lufenuron in the treatment of feline dermatophytosis. Forty‐six cats (Persians and mixed‐breed cats from 1‐month to 4‐years old) naturally infected with Microsporumcanis were included in this study. Fifteen cats were treated isolated in cages in the veterinary hospital and 31 were treated in their home environment (some with access to the outdoors). Dermatophyte skin lesions were seen in 29 animals while 17 other cats were asymptomatic carriers. Wood's lamp, direct microscopic examination of hairs, fungal culture and skin biopsies were used for the diagnosis. Affected cats and all in‐contact animals received lufenuron at a dose of 120 mg/kg every 21 days for four treatments. Of the 29 symptomatic cats treated with lufenuron, 70% recovered within 21 days and 28% within 42 days of initiation of therapy. One cat had only partial recovery and another was euthanized. Negative fungal culture was recorded only after the fourth dose of lufenuron in 98% of affected cats and 100% of asymptomatic carriers. There was no difference in clinical response to lufenuron between the cats treated in their home environment and those treated in the veterinary hospital. Side effects were not observed, thus the drug proved to be safe and effective for the treatment of dermatophytosis. Funding: Novartis.     

Efficacy of a novel formulation of metaflumizone for the control of fleas (Ctenocephalides felis) on cats

A novel spot-on formulation containing metaflumizone (ProMeris for Cats, Fort Dodge Animal Health, Overland Park, KS) was evaluated in five laboratory studies to determine the duration of residual efficacy in cats against fleas after a single spot treatment. In each study, eight domestic shorthair cats were randomly allocated to each treatment group and individually housed. One group in each study remained non-treated. In one study, an additional group of eight cats was treated with a placebo formulation. Cats were treated topically with metaflumizone formulation to provide a dose of at least 40mg metaflumizone/kg. Cats were infested with 100 cat fleas (Ctenocephalides felis felis) once per week for approximately 8 weeks. Cats were comb counted 48h after treatment and each infestation to determine the number of viable fleas present. There were no significant differences in flea counts between the non-treated control and the placebo-treated control (P>0.05) other than a 26% reduction at week 1, demonstrating that the formulation excipients had no activity. Metaflumizone treatment resulted in significantly lower flea numbers relative to non-treated controls on all post-treatment count days (P<0.05). Metaflumizone provided >90% control of flea infestations up to 7 weeks following a single treatment.     

Dose selection of selamectin for efficacy against adult fleas (Ctenocephalides felis felis) on dogs and cats

Selamectin, a novel avermectin, was evaluated in two controlled studies (one in Beagles, one in domestic shorthaired cats) to determine an appropriate topical dose for efficacy against adult Ctenocephalides felis felis (C. felis) fleas on dogs and cats for 1 month. For each study, animals were allocated randomly to four treatments. One treatment consisted of the inert formulation ingredients (vehicle) administered as a negative control, and the other three treatments consisted of a single topical dosage of 3, 6, or 9mgkg(-1) of selamectin. In each study, selamectin was administered as a topical dose applied to the skin in a single spot at the base of the neck in front of the scapulae. Dogs and cats were infested with 100 viable unfed C. felis (50 males and 50 females) on days 4, 11, 18, and 27. Seventy-two hours (+/-2h) after each infestation, on days 7, 14, 21, and 30, a comb count to determine the number of viable fleas present on each animal was performed. Efficacy of selamectin on day 30 was used to select an appropriate dose. For dogs and cats, percentage reductions in geometric mean flea comb counts for the three selamectin treatments ranged from 94. 6 to 100% on days 7, 14, and 21, compared with the negative-control treatment. On day 30, reductions in flea comb counts were 81.5, 94.7, and 90.8% for dogs, and 79.8, 98.0, and 96.2% for cats treated with selamectin at 3, 6, or 9mgkg(-1), respectively. For day 30 flea comb counts for dogs and cats, analysis of variance showed that the three selamectin treatments resulted in significantly (P< or =0.05) lower counts than did the negative-control treatment. For dogs and cats, geometric mean flea counts for selamectin administered at a dosage of 3mgkg(-1) were significantly (P< or =0.05) higher than those for the 6 and 9mgkg(-1) treatment dosages combined. There were no significant differences in flea counts between the 6 and 9mgkg(-1) treatments. This analysis was confirmed by linear-plateau modeling. Thus, the optimal dose of selamectin for efficacy against adult fleas for both dogs and cats, as estimated by the turning point (plateau) in the dose response curve, was 6mgkg(-1).     

Fatal anemia and dermatitis in captive agoutis (Dasyprocta mexicana) infested with Echidnophaga fleas

Two captive agoutis (Dasyprocta mexicana) died of anemia with centrilobular hepatocellular necrosis (2/2), severe flea ectoparasitism (2/2), and cardiomegaly attributed to anemia (1/2). Other agoutis were similarly parasitized and one had anemia. Fleas were manually removed and all agoutis treated topically with propoxur and selamectin and moved to another enclosure. No additional cases of fatal anemia were seen. Cutaneous lesions suggestive of hypersensitivity were observed in three additional agoutis with dorsal alopecia (3/3), a penetrating wound associated with pruritus and self-mutilation in the flank (2/3), flea ectoparasitism at the time of morphologic diagnosis (1/3), and hyperplastic perivascular dermatitis (3/3). One of these died of bacterial infection of the wound. Similar but milder skin disease was seen in 3 out of over 30 maras (Dolichotis patagonum) housed in the same exhibit. Fleas collected from all the fatal agouti cases and maras were classified in the genus Echidnophaga based on the angular front margin of head, contracted thorax, absence of genal and pronotal combs, and the fact that fleas did not jump. These findings suggest that flea ectoparasitism may be an important cause of morbidity and mortality in captive rodents.     

Pharmacokinetic study of an injectable long-acting parenteral formulation of doxycycline hyclate in calves

Doxycycline hyclate (DOX-h) can be regarded as a time-dependant antibacterial. Hence, a parenteral long-acting formulation may be regarded as more pharmacologically sound. A poloxamer-based matrix was used to produce a long-acting injectable preparation (DOX-h-LA) and its serum concentrations vs. time profile investigated after its s.c. injection to calves. Serum concentrations profiles for such a prepartion were compared to the corresponding profiles obtained with an aqueous formulation of DOX-h injected either i.m. or i.v. in 10 calves in a crossover study at dose of 10mg/kg, with washout periods. DOX-h-LA showed the greatest values for bioavailability (602%); maximum serum concentration (C(max)) value was 1.99microg/mL with a time to reach C(max) (T(max)) of 25h and an elimination half-life of 40.81h. Considering minimum effective serum concentration of 0.5microg/mL a dose-interval of 80h can be achieved for DOX-h-LA, and only 9.7h and 17h after the i.v. or i.m. administration of DOX-h, respectively.     

Control of fleas on pets and in homes by use of imidacloprid or lufenuron and a pyrethrin spray.

OBJECTIVE: To evaluate imidacloprid and the combination of lufenuron and pyrethrin to control flea infestations in households with pets. ANIMALS: 37 dogs and 19 cats in 34 flea-infested households. PROCEDURE: Households were assigned randomly to 1 of 2 groups. Pets in group 1 were treated topically with imidacloprid on day 0, then once a month for 90 days. Pets in group 2 were given lufenuron orally on day 0 and at monthly intervals for 90 days and also were treated topically with a pyrethrin spray every 1 to 2 weeks throughout the study. Flea numbers in homes were assessed by use of intermittent light traps, and flea burdens on pets were assessed using visual area counts done once a week during the first month, then every other week. RESULTS: One application of imidacloprid reduced flea burdens on pets by 96 and 93.5% on days 7 and 28, respectively, compared with day-0 burdens. Following 3 applications, flea burdens on pets and in homes were reduced by 98.8 and 99.9%, respectively. Lufenuron and pyrethrin spray reduced flea numbers on pets by 48.9 and 91.1% on days 7 and 28, respectively. By the end of the study, this combination reduced flea burdens on pets and in homes by 99.2 and 99.7%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Imidacloprid applied topically or lufenuron administered orally along with a topically applied pyrethrin spray were effective in eliminating fleas on pets and in homes. Flea control can be achieved with topical application of adulticides or oral administration of insect growth regulators without concomitant treatment of the surroundings.     

Streptokinase treatment of cats with experimentally induced aortic thrombosis

An investigation was initiated to determine the dosage of streptokinase (given IV) that would consistently produce systemic fibrinolysis, as determined by laboratory evaluation, and to determine the relative safety of this drug in the cat. Results indicated that a loading dose of 90,000 IU of streptokinase (given by continuous infusion over 20 to 30 minutes) and a maintenance dosage (IV) of 45,000 IU of streptokinase/hr predictably produced systemic fibrinolysis in the cat. There were no detectable adverse affects seen on physical examination, necropsy, or histopathologic examination. Using the foregoing dosage regimen, investigation was begun to evaluate the use of streptokinase for treatment of feline thromboembolism. Aortic thrombosis was created experimentally in 15 cats. There was no clearly predictable improvement in nonspecific venous angiograms or thermal circulatory indices for the cats given streptokinase, compared with the values for the control cats. After a total of 180 minutes of treatment, the mean weight of remaining clot removed at necropsy from the aortic trifurcation was 7.3 mg in the streptokinase-treated cats, compared with 13.4 mg in the control cats.     

Comparison of the activity of selamectin, imidacloprid and fipronil for the treatment of cats infested experimentally with Ctenocephalides felis felis and Ctenocephalides felis strongylus

Twenty adult, domestic short hair cats were randomly allocated into four groups of five cats and housed in separated cages. Each cat was infested with 25 fleas Ctenocephalides felis felis and 25 Ctenocephalides felis strongylus and 2 days later (day 0) the cats in group 1, 2 and 3 received a spot on application of selamectin, imidacloprid or fipronil, respectively, while the cats in group four were not treated. The cats were combed 48 h later, the fleas were removed, counted and their subspecies were determined. All the cats were reinfested with the same number of the two subspecies of fleas on days 7, 14, 21, 29 and 35. The efficacy of each treatment was calculated 48 h after each infestation. The mean number of fleas on the control cats was 16.4 C. f. felis and 13.4 C. f. strongylus. The three treatments were effective for the first 31 days for C. f. felis and for the full 37 days for C. f. strongylus. Over the first 31 days, the efficacy of selamectin ranged from 89 to 100% and 85 to 100% against C. f. felis and C. f. strongylus, respectively, the efficacy of imidacloprid ranged from 76 to 100% and 92 to 100% and the efficacy of fipronil ranged from 98 to 100% and 97 to 100% against C. f. felis and C. f. strongylus. There were no significant differences between the control of C. f. felis and C. f. strongylus by the three products.