P‐26 New aspects of canine demodicosis and the possibility of treatment with selamectin

The purpose of this study was to evaluate 55 clinical cases of canine demodicosis and to compare the results of treatment using amitraz (solution), selamectin (spot‐on), ivermectin (injection) and cythioate (oral tablets). Data from the 55 cases was collected and evaluated after clinical and microbiological examination. Treatment was selected depending on the severity of demodicosis and compliance of the owner. The cases were followed for 12 months and the status of the patients was grouped on two levels: recovered (58%), or relapsed (42%). Five dogs (9%) were euthanized. The disease was commonly diagnosed in purebred dogs. Demodicosis was more common in dogs under 2 years of age (65%), in males (64%), and in the short‐haired breeds (75%). Demodicosis was generalized in 73% of cases, localised in 23% and affected the feet (pododemodicosis) in 4% of cases. Recovery was the highest in dogs between 1 and 2 years of age (73%), and in the localized cases (92%). Nonspecific treatment with glucocorticoids prior to the diagnosis lowered the rate of recovery (4%), but treatment with glucocorticoids for proven atopic dermatitis improved the rate of recovery (41%). All drugs (amitraz, selamectin, cythioate) administered for the localized form were effective (100% recovered). Recovery in generalized demodicosis was 60% using ivermectin, 55% using amitraz, 44% with the combination of amitraz and selamectin (two treatments with amitraz followed by selamectin), and 43% in cases where selamectin was used alone. Funding: Pfizer Animal Health.     

Treatment protocols for demodicosis: an evidence-based review

Publications discussing the treatment of demodicosis in the dog and cat are reviewed. Based on the evidence in the literature, amitraz rinses at 0.025-0.06% every 7-14 days, and oral daily ivermectin at 300 micro g kg(-1), milbemycin at 2 mg kg(-1) and moxidectin at 400 micro g kg(-1), respectively, can all be recommended for the treatment of generalized canine demodicosis. Ivermectin and moxidectin should be initiated at lower doses and patients monitored for possible adverse effects during therapy. In cats, 2% lime sulfur dips and amitraz rinses at 0.0125-0.025% have been used successfully.     

Brain penetration of ivermectin and selamectin in mdr1a,b P-glycoprotein- and bcrp- deficient knockout mice

P-glycoprotein, which is encoded by the multi-drug resistance gene (MDR1), highly restricts the entry of ivermectin into the brain by an ATP-driven efflux mechanism at the blood–brain barrier. In dogs with a homozygous MDR1 mutation though, ivermectin accumulates in the brain and provokes severe signs of neurotoxicosis and even death. In contrast to ivermectin, selamectin is safer in the treatment of MDR1 mutant dogs, suggesting that selamectin is transported differently by P-glycoprotein across the blood–brain barrier. To test this, we applied selamectin to mdr1-deficient mdr1a,b ^−/− knockout mice and wild-type mice. Brain penetration, organ distribution, and plasma kinetics were analyzed after intravenous, oral, and dermal spot-on application in comparison with ivermectin. We found that in vivo both macrocyclic lactone compounds are substrates of P-glycoprotein and that these strongly accumulate in the brain of mdr1a,b ^−/− knockout mice compared with wild-type mice at therapeutic doses of 12 mg/kg selamectin and 0.2 mg/kg ivermectin. However, selamectin accumulates to a much lesser degree (5–10 times) than ivermectin (36–60 times) in the absence of P-glycoprotein. This could explain the broader margin of safety of selamectin in MDR1 mutant dogs. In liver, kidney, and testes, ivermectin and selamectin accumulated less than four times as much in mdr1a,b mutant mice as in wild-type mice. Breast cancer resistance protein (Bcrp)-deficient bcrp ^−/− knockout mice were also included in the application studies, but showed no differences in brain concentrations or organ distribution of either ivermectin or selamectin compared with wild-type mice. This indicates that Bcrp is not a relevant efflux carrier for these macrocyclic lactone compounds in vivo at the blood–brain barrier.     

Treatment of demodicosis in dogs: 2011 clinical practice guidelines

Background and Objectives – These guidelines were written by an international group of specialists with the aim to provide veterinarians with current recommendations for the diagnosis and treatment of canine demodicosis. Methods – Published studies of the various treatment options were reviewed and summarized. Where evidence in form of published studies was not available, expert consensus formed the base of the recommendations. Results – Demodicosis can usually be diagnosed by deep skin scrapings or trichograms; in rare cases a skin biopsy may be needed for diagnosis. Immune suppression due to endoparasitism or malnutrition in young dogs and endocrine diseases, neoplasia and chemotherapy in older dogs are considered predisposing factors and should be diagnosed and treated to optimize the therapeutic outcome. Dogs with disease severity requiring parasiticidal therapy should not be bred. Secondary bacterial skin infections frequently complicate the disease and require topical and/or systemic antimicrobial therapy. There is good evidence for the efficacy of weekly amitraz rinses and daily oral macrocyclic lactones such as milbemycin oxime, ivermectin and moxidectin for the treatment of canine demodicosis. Weekly application of topical moxidectin can be useful in dogs with milder forms of the disease. There is some evidence for the efficacy of weekly or twice weekly subcutaneous or oral doramectin. Systemic macrocyclic lactones may cause neurological adverse effects in sensitive dogs, thus a gradual increase to the final therapeutic dose may be prudent (particularly in herding breeds). Treatment should be monitored with monthly skin scrapings and extended beyond clinical and microscopic cure to minimize recurrences. Editor’s Note – A brief review article by R. Mueller has been published: Evidence‐based treatment of canine demodicosis, Tierarztl Prax Ausg K Kleintiere Heimtiere 2011; 39: 419–24. This is not considered to constitute duplication of the article published here in Veterinary Dermatology.     

Comparative speed of kill between nitenpyram,fipronil, imidacloprid,selamectin and cythioate against adult Ctenocephalides felis (Bouché) on cats and dogs

Speed of kill and percentage kill of nitenpyram (CAPSTAR) was compared to fipronil (Frontline) spot-on), imidacloprid (Bayvantage/Advantage), selamectin (Stronghold/Revolution) and cythioate (Cyflee) against adult fleas on cats and dogs 3 and 8h post-treatment. Selamectin was used on dogs only; cythioate was used on cats only. Groups of eight cats and eight dogs (four males and four females each) were experimentally infested with 100 unfed fleas 1 day prior to treatment with the test products. One group of cats and one group of dogs served as control. Fleas were collected from four cats and four dogs in each group (two males and two females) by combing 3h after treatment, the remaining four cats or dogs were combed 8h after treatment. In cats cythioate treatment resulted in a mean efficacy of 62.4 and 97.4% at 3 and 8h post-treatment, respectively. Imidacloprid efficacy at the same times was 26.9 and 82.8%, whereas fipronil efficacy was 24.3 and 62.6% efficacy, respectively. In dogs mean efficacy 3 and 8h after treatment with selamectin was 39.7 and 74.4%; with imidacloprid efficacy was 22.2 and 95.7%, respectively and 35.9 and 46.5%, respectively after treatment with fipronil. Nitenpyram was 100% effective in cats and 99.1% effective in dogs within 3h of treatment and 100% effective in cats and dogs within 8h.     

Efficacy of daily oral ivermectin in the treatment of 10 cases of generalized demodicosis in adult dogs

Abstract The purpose of this study was to evaluate the efficacy of oral ivermectin at the dosage of 0.35 mg kg^-1 day^-1 for the treatment of generalized demodicosis in 10 adult dogs. Five of these 10 dogs had failed to respond to previous topical amitraz therapy. The mean time to obtain negative skin scrapings was 2.7 months and the mean duration of treatment was 4 months (range 2.5–8.5 months). Three patients (30%) were cured and they remained free of mites within 1 year follow-up. Two dogs (20%) were in remission for less than 6 months and five dogs (50%) relapsed. These five cases that relapsed were retreated with the above dosage of ivermectin and topical amitraz solution (1 mL Taktic/30 mL mineral oil) applied to site(s) of recurrence. One of these five cases that relapsed was in remission for more than 6 months, two dogs were in remission for less than 6 months and two dogs are still receiving treatment. Résumé— Le propos de cette étude est d'évaluer l'efficacieté de l'ivermectine par voie orale à un dosage de 0,35 mg/kg/jour dans le traitement de la démodécie généralisée chez 10 chiens adultes. Cinq de ces chiens n'avaient pas répondu à une thérapeutique topique préalable à l'amitraz. Le délai moyen pour obtenir la négativation des raclages cutanés est de 2,7 mois, et la durée moyenne de traitement est de 4 mois (extrême 2,5–8,5 mois). Trois patients (30%) ont été guéris et n'ont pas rechuté dans l'année qui a suivi le traitement. Deux des chiens (20%) ont été en rémission pendant moins de 6 mois et 5 chiens (50%) ont rechuté. Ces 5 chiens qui ont rechuté ont été retraités avec l'ivermectine à la même posologie associée à une thérapeutique topique à l'amitraz (1 ml de Taktic dans 30 ml d'huile minérale), appliquée aux sites de rechute. Un de ces 5 chiens fut en rémission pendant plus de 6 mois, 2 chiens pendant moins de 6 mois, enfin, les deux derniers reçoivent encore le traitement. [Fondati, A. Efficacy of daily oral ivermectin in the treatment of 10 cases of generalized demodicosis in adult dogs (Efficacité de l'ivermectine administrée oralement tous les jours dans le traitement de 10 cas de démodécie généralisée du chien adulte). Veterinary Dermatology 1996; 7 : 99–104.] Resumen El objetivo de este estudio fue evaluar la eficacia de la ivermectina oral con una dosis de 0.35 mg/Kg-dia para el tratamiento de la demodicosis generalizada en 10 perros adultos. Cinco de los 10 perros no habian respondido previamente a la terapia tópica con amitraz. El tiempo medio de obtención de raspados cutáneos negativos fue de 2.7 meses y la duratión media del tratamiento, de 4 meses (de 2.5 a 8.5 meses). Tres pacientes (30%) se curaron y permanecieron sin ácaros en un año de seguimiento. Dos perros (20%) estuvieron en remisión durante menos de 6 meses y en cinco (50%) se produjeron recaidas. Los animales que recayeron fueron tratados con la dosis de Ivermectina especificada arriba y solutión tópica de amitraz (1 mL Taktic/30 mL aceite mineral) aplicado a la(s) zona(s) de recidiva. Uno de los casos que recayó había estado en remisión durante 6 meses, dos perros estuvieron en remisión durante menos de 6 meses y dos estan aún bajo tratamiento. [Fondati, A. Efficacy of daily oral ivermectin in the treatment of 10 cases of generalized demodicosis in adult dogs (Eficacia de la Ivermectina oral en dosis diarias en el tratamiento de 10 casos de demodicosis generalizada en perros adultos). Veterinary Dermatology 1996; 7 : 99–104.] Zusammenfassung— Zweck dieser Studie war, die Wirksamkeit von oralem Ivermectin mit einer Dosierung von 0,35 mg/kg und Tag bei der Behandlung von generalisierter Demodikose bei 10 erwachsenen Hunden auszuwerten. 5 dieser 10 Hunden hatten auf eine vorausgegangene topische Amitraz-Therapie nicht angesprochen. Die Durchschnittszeit, um negative Hautgeschabsel zu erhalten, lag bei 2,7 Monaten, die Durchschnittsdauer der Behandlung bei 4 Monaten (mit einer Spannweite von 2,5 bis 8,5 Monaten). 3 Patienten (30%) wurden geheilt und blieben innerhalb des überwachungszeitraumes von 1 Jahr milbenfrei. Zwei Hunde (20%) waren in Remission für weniger als 6 Monate und 5 Hunde (50%) hatten ein Rezidiv. Diese fünf Rezidivfälle wurden mit der oben genannten Dosis Ivermectin und topischer Amitraz-Lösung (1 ml Taktic/30 ml Mineralöl) an den Stellen erneuter Veränderungen behandelt. Einer dieser fünf Rezidivfälle war in Remission für mehr als 6 Monate, zwei Hunde waren in Remission für weniger als 6 Monate und zwei Hunde sind immer noch unter Therapie. [Fondati, A. Efficacy of daily oral ivermectin in the treatment of 10 cases of generalized demodicosis in adult dogs (Wirksamkeit einer täglichen oralen Ivermectingabe bei der Behandlung von 10 Fällen von generalisierter Demodikose bei erwachsenen Hunden). Veterinary Dermatology 1996; 7 : 99–104.]     

Efficacy of daily amitraz on generalised demodicosis in dogs

Fifty dogs with generalised demodicosis were treated with daily applications of 0·125 per cent amitraz solution over half the body. This was applied once a day, alternating the body half treated. Nine dogs were lost to follow-up; the remaining dogs were classified as either a success (25 dogs, 61 per cent) or a failure (16 dogs, 39 per cent) according to their response to treatment. Eight of the failures were due to persistent demodicosis and eight relapsed within one year after treatment. All eight of the relapsed dogs were cured after a second course of daily amitraz treatment. For the 25 dogs considered treatment successes, the median duration of treatment was 6·5 weeks (range, three weeks to nine months), and the median interval from completion of treatment to last post treatment evaluation was 3·4 years (range, two to four-and-a-half-years). Including the eight dogs that were cured after retreatment, the daily amitraz applications were curative in 33 of 41 dogs (80 per cent) with generalised demodicosis.     

Efficacy of 1.25% amitraz solution in the treatment of generalized demodicosis (eight cases) and sarcoptic mange (five cases) in dogs

Eight dogs with generalized demodicosis and five with sarcoptic mange were treated with 1.25% amitraz solution applied weekly and associated with an antidote treatment (atipamezol, 0.1 mg kg⁻¹ IM once: and yohimbine 0.1 mg kg⁻¹ once daily for 3 days, orally). Results of skin scrapings were used to determine whether therapy should be continued or stopped. The median number of treatments for demodicosis and sarcoptic mange was three (range 2–5) and two (range 1–3), respectively. Some side-effects were observed but all were stopped with antidote treatment; no failure or relapses occurred at 6–36 months after treatment.     

Changes in oxidative stress indices, zinc and copper concentrations in blood in canine demodicosis

Status of certain oxidative stress indices and zinc and copper concentrations in blood were estimated in dogs with localized demodicosis (LD) and generalized demodicosis (GD). In comparison to healthy control, erythrocytic lipid peroxides level and superoxide dismutase activity were significantly (P < 0.01) higher in both LD as well as GD. However, level of reduced glutathione and activity of catalase were significantly (P < 0.01) lower in both LD and GD. Blood zinc and copper levels in dogs with LD and GD were significantly (P < 0.01) lower than healthy control. Significant (P < 0.01) differences were also observed in different oxidative stress indices and zinc and copper levels in between LD and GD groups. From the present study, it was concluded that demodicosis is associated with oxidative stress and antioxidant supplementation may be beneficial in management of canine demodicosis.     

药物治疗犬疥螨病比较试验

为了评估对犬疥螨病的治疗效果,将80只确诊为犬疥螨病的病犬随机分为4组,每组20只.第1组用阿维菌素加杀螨灵治疗；第2组用阿维菌素加双甲脒治疗；第3组用伊维菌素加杀螨灵治疗；第4组用伊维菌素加双甲脒治疗.结果表明,第1组治愈率为85％,第2组治愈率为80％,第3组治愈率为90％,第4组治愈率为95％.结果表明第4组的治...     

Topical (pour-on) ivermectin in the treatment of chronic generalized demodicosis in dogs

Twelve privately owned dogs with chronic generalized demodicosis were treated topically along the dorsal midline with 1.5 mg kg⁻¹ of 0.5% pour-on ivermectin for cattle three times per week for 3–6 months. All 12 dogs had a substantial reduction in clinical signs and in the number of Demodex canis mites found on skin scrapings. Only two dogs, however, became skin-scrapings negative after 3 and 5 months of treatment, respectively. In these two dogs treatment was prolonged for an additional 4 weeks past the negative scrapings. One dog relapsed 2 months after cessation of therapy; the other is still free of symptoms 1.5 years later. The cure rate, based on the lack of recurrence of clinical signs for 12 months after discontinuation of ivermectin administration, was 1 of 12 dogs (8%). Adverse reactions were not seen.     

Repellency and efficacy of 65% permethrin and selamectin spot-on formulations against Ixodes ricinus ticks on dogs

Two topically applied spot-on products used for flea and tick control on dogs, 65% permethrin (Defend EXspot Treatment for Dogs, Schering-Plough Animal Health Corp., Union, NJ) and selamectin (Revolution [United States] or Stronghold [Europe], Pfizer Animal Health, New York, NY), were evaluated for repellency and efficacy against Ixodes ricinus, the primary vector of Lyme disease in Europe. Eighteen dogs were evenly and randomly allocated to the following treatments: 1) 65% permethrin, 2) selamectin, 3) untreated control. Dogs were treated by topical application of the assigned product in accordance with product label directions on Day 0. At 7, 14, 21, 28, and 35 days after treatment, each dog was exposed for 2 hours to 50 unfed, adult ticks in a cage with a carpet that covered approximately 70% of the floor area. After the exposure period, dogs were removed from the cages and live and dead ticks were counted on the dogs and in the cages. The number of live ticks recovered was reduced by 90.3% to 99.5% for dogs treated with 65% permethrin (P <.0001 versus controls and selamectin), compared with 10.9% to 31.1% for dogs treated with selamectin (P >.05 versus controls). The repellency of 65% permethrin was 63.4% to 80.2% against I. ricinus ticks (P <.0001 versus controls, P <.0007 versus selamectin), compared with 0% to 10.9% repellency for selamectin (P >.05 versus controls).     

Efficacy of selamectin in the prevention of adult heartworm (Dirofilaria immitis) infection in dogs in northern Italy

The efficacy of a novel avermectin, selamectin, was evaluated for the prevention of heartworm disease (adult Dirofilaria immitis infection) in 120 dogs (aged 9 months to 13 years at enrolment) presented as veterinary patients. The study was conducted at five veterinary practices in a heartworm hyperendemic region of northern Italy. Dogs were allocated randomly in a 2:1 ratio to treatment with either selamectin or ivermectin. Treatments were administered at monthly intervals for 6 months during the heartworm transmission season (May-November). Selamectin was applied topically in a single spot to the skin on each animal's back at the base of the neck in front of the scapulae as a unit dose that provided at least the minimum recommended dosage of 6mgkg(-1) (range, 6-12mgkg(-1)). Ivermectin (6microgkg(-1) of body weight) was administered orally at monthly intervals, in accordance with the manufacturer's product label recommendations. Study day 0 was defined individually for each dog as the day of first treatment administration. Efficacy was assessed on the basis of the absence of D. immitis microfilariae and adult heartworm (D. immitis) antigen in tests conducted on days 180 and 300. There were no adverse clinical signs arising due to treatment with selamectin and no drug-related mortalities. The prevention rate for D. immitis microfilariae and adult heartworm antigen was 100% for both selamectin and ivermectin. Thus, selamectin administered as a unit dose, providing at least the recommended minimum dosage of 6mgkg(-1), at monthly intervals during the heartworm transmission season was safe and 100% effective in the prevention of heartworm disease in dogs presented as veterinary patients.     

Adult-onset demodicosis in two dogs due to Demodex canis and a short-tailed demodectic mite

Infestation with a short-tailed demodectic mite and Demodex canis was diagnosed in both a six-and-a-half-year-old and a four-year-old dog. The clinical picture was compatible with generalised demodicosis complicated by staphylococcal pyoderma (case 1), or localised demodicosis (case 2). In both cases, the short-tailed demodectic mite outnumbered D canis in superficial skin scrapings. The laboratory findings (lymphopenia, eosinopenia, increased serum alkaline phosphatase and alanine aminotransferase activities, diluted urine and proteinuria) and the results of a low dose dexamethasone suppression test were suggestive of underlying hyperadrenocorticism in the first case. Hypothyroidism was considered a possibility in the second case, owing to the sustained bradycardia and the extremely low basal total thyroxine value. Systemic treatment with ivermectin and cephalexin (case 1), or topical application of an amitraz solution in mineral oil, along with sodium levothyroxine replacement therapy (case 2), resulted in a complete resolution of the skin lesions and the disappearance of both types of demodectic mite after two and one and a half months, respectively.     

The role of apoptosis in immunosuppression of dogs with demodicosis

The aim of the present study was to evaluate the status of apoptosis in peripheral blood leukocytes of dogs with demodicosis. A total of 26 dogs suffering from demodicosis, and positive for Demodex canis mites by skin scraping, participated in the study, 13 with localized demodicosis (LD) and 13 with generalized demodicosis (GD). A further 13 clinically healthy dogs, all of whom were negative for mites upon skin scraping, were used as controls. The dogs with GD revealed significantly higher (P ≤ 0.0001) percentage of leukocytes with externalization of phosphatidylserine (PS) and depolarized mitochondrial membrane potentials (ΔΨm) as compared with the dogs with LD and healthy controls. These dogs also revealed significantly lower values (P ≤ 0.0001) of hematological parameters viz. hemoglobin, total erythrocytes count total leukocytes count, lymphocytes, monocytes and neutrophils. Significantly higher (P ≤ 0.0001) percentages of leukocytes with externalization of PS and depolarized ΔΨm were also found in dogs with LD as compared with the healthy controls. These dogs also revealed significantly lower values of Hb (P ≤ 0.0001), TEC (P=0.025), TLC (P ≤ 0.0001), lymphocytes (P=0.008), monocytes (P ≤ 0.0001) and neutrophils (P=0.03). It is concluded that premature apoptosis of PBL may be implicated in the immunosuppression of the dogs with demodicosis.     

Evaluation of a topical treatment, alone and in combination with a detergent, for generalized demodicosis

Thirty dogs (20 treated, 10 controls) with naturally-acquired generalized demodicosis were utilized to evaluate the bio-activity and safety of a liquid concentrate formulation of amitraz, with or without the addition of a nonionic detergent. The detergent was added to the treatment mixture to enhance wetting and thereby reduce the number of treatments required to return diseased animals to a normal state. Three--six miticide treatments were topically applied to dogs at 14-day intervals, at a concentration of 250 parts per million active drug. The liquid concentrate with or without detergent, was equally effective and safe as a dermatotherapy for demodicosis; addition of the nonionic detergent grossly improved the wetting characteristics of the treatment mixture; however, it did not alter the biological activity or the safety of the therapy.     

New approaches to the treatment of canine demodicosis.

Topical amitraz is the only approved treatment for CGD; however, it is not always effective or well tolerated. Extra-label use of amitraz, milbemycin oxime, ivermectin, and moxidectin may be effective therapeutical alternatives for dogs with resistant CGD or dogs that have an intolerance to the licensed amitraz protocol. It appears that oral administration of milbemycin oxime (1-2 mg/kg), ivermectin (400-600 micrograms/kg), and moxidectin (400 micrograms/kg) daily is a practical therapeutical alternative and would provide similar cure rates. Nevertheless, milbemycin oxime is expensive, ivermectin is potentially more toxic, and only limited information is available on moxidectin. The average treatment duration with these new regimens is 4 months, with an expected range of 3 to 10 months. Treatment should be administered daily for a minimum of 3 months and for at least 1 month after a series of negative skin scrapings. For chronic cases or cases that take a relatively long time to respond to therapy, 2 to 3 months of treatment beyond negative scrapings may be more appropriate. Dogs with CGD always approach clinical normalcy weeks to months before negative skin scrapings are obtained. All dogs respond at their own rate; as long as the skin scrapings at each visit show fewer mites, the current therapy should be continued for an additional month. If the mite count starts to increase, this may suggest that the treatment protocol is not being followed or it may be that the therapy chosen was suboptimally effective. Although CGD is still a disease that is not easily treated, the prognosis for dogs with this disorder has dramatically improved in the past few years. It must be remembered, however, that the treatment alternatives for CGD described above are not approved and should not be used unless the approved therapeutical regimen has failed.     

Localised sarcoptic mange in dogs: a retrospective study of 10 cases

The authors report 10 cases of localised sarcoptic mange in dogs. In each case, lesions were localised to one precise area of the skin. Pruritus was present in nine cases and absent in one. Affected areas were the feet (one case), the face and/or the pinnae (six cases), the abdominal skin (one case), the flank (one case) and the lumbar area (one case). The types of lesions were erythema, papules, lichenification, scales, crusts and alopecia. Parasites were found in all cases except one, in which anti-immunoglobulin G Sarcoptes serology was positive. The acaricidal treatments given were lindane, ivermectin or selamectin and were all successful.     

P-23 Clinical and epidemiological characteristics of 153 cases of Sarcoptic acariosis in dogs

A randomized and controlled field study was performed in canine patients to evaluate the efficacy of selamectin in the treatment of naturally occurring Sarcoptes scabiei and Otodectes cynotis infestations in dogs. A total of 227 dogs from six veterinary practices in South Korea were included. Dogs were randomly assigned to treatment with selamectin or a positive-control product. Selamectin was administered as a unit dose providing a minimum of 6 mg/kg in a topical preparation applied to the skin in a single spot on days 0 and 30 [ S. scabiei ( n =  113) and O. cynotis ( n =  114)]. The presence of parasites was assessed before treatment and at 14, 30 and 60 days after the initiation of treatment. The animals were evaluated clinically at each assessment period. Based on skin scrapings, the efficacy of selamectin against S. scabiei infestations on dogs was >95% by day 30, and 100% by day 60. Against O. cynotis , selamectin eliminated mites in 100% of dogs by day 60. However, clinical signs of pruritus, erythema, scale, and crusted papules did not diminish concomittantly with resolution of S. scabiei in skin scrapings. The positive-control products achieved similar results. Therefore, selamectin was safe and effective against sarcoptic mange and ear mites in dogs.
Funding: Pfizer Animal Health.     

Selamectin is a potent substrate and inhibitor of human and canine P-glycoprotein

The transport of the antiparasitic agents, ivermectin, selamectin and moxidectin was studied in human intestinal epithelial cell monolayers (Caco-2) and canine peripheral blood lymphocytes (PBL). Both models expressed the mdr1-coded 170 kDa ATP-binding cassette (ABC) transporter P-glycoprotein (P-gp). Fluxes of the P-gp substrate rhodamine-123 (Rh-123) across Caco-2 monolayers showed that ivermectin and selamectin acted as potent P-gp inhibitors with IC50 values of 0.1 microm. In contrast, moxidectin was a weaker P-gp inhibitor with an IC50 of 10 microm. The transport of radiolabelled ivermectin, selamectin and moxidectin through Caco-2 monolayers showed that ivermectin, selamectin and moxidectin were P-gp substrates with secretory/absorptive ratios of 7.5, 4.7 and 2.6 respectively. Secretory transport of [3H]-ivermectin and [3H]-selamectin was blocked by the P-gp inhibitor, verapamil. Ivermectin and selamectin inhibited the efflux of Rh-123 from PBL and the concentration of inhibition was similar to that of verapamil. In contrast, moxidectin did not have a significant effect on Rh-123 efflux from PBL. The data suggest that ivermectin and selamectin are potent P-gp substrates, while moxidectin is a weak one.