BackgroundLotilaner is a novel isoxazoline developed for oral administration to dogs. In laboratory studies, lotilaner was shown to be safe and to produce a rapid flea and tick knockdown, with a sustained speed of kill for at least a month post-treatment. A study was undertaken to demonstrate the efficacy, safety and palatability of three monthly doses of lotilaner flavoured chewable tablets (Credelio™, Elanco) in controlling fleas under field conditions in Europe.MethodsDogs were enrolled at 17 veterinary clinics across Germany, Hungary and Portugal. Qualifying households having no more than three dogs and one primary dog with at least five fleas was randomised 2:1 to a lotilaner (minimum dose rate 20 mg/kg) or a topical fipronil group (administered per label). There were 128 and 64 households allocated to the lotilaner and fipronil groups, respectively. Treatments were dispensed to owners on Days 0, 28 and 56; supplementary household dogs received the same treatment as the primary dog. Post-enrollment flea counts and flea allergy dermatitis (FAD) assessments were made on primary dogs on Days 14, 28, 56 and 84. Efficacy calculations were based on geometric mean percent reductions of live flea counts versus pre-treatment counts on Day 0. The safety and palatability of lotilaner tablets were also assessed.ResultsLotilaner efficacy was 99.1, 99.5, 99.9 and 99.8% on Days 14, 28, 56 and 84, respectively. Corresponding reductions for fipronil were 93.4, 91.2, 94.4 and 97.0%. Lotilaner was superior to fipronil at all post-Day 0 assessments (t (186) ≥ 3.43, P ≤ 0.0007). At every post-treatment assessment, at least 90% of lotilaner-treated dogs were flea-free (98.4% on Day 84); fewer than 90% of fipronil group dogs were flea-free on the same time points. Lotilaner flavoured chewable tablets were palatable, and both products were well tolerated. Lotilaner alleviated or eliminated clinical signs of FAD, including pruritus.ConclusionsUnder field conditions in Europe, lotilaner flavoured chewable tablets were greater than 99% effective in eliminating fleas from dogs at the first post-treatment assessment (Day 14). Efficacy was maintained through Day 84, with corresponding improvements in FAD. Lotilaner tablets were palatable and safe and provided superior flea control to fipronil.Electronic supplementary materialThe online version of this article (10.1186/s13071-017-2479-8) contains supplementary material, which is available to authorized users.

BackgroundLotilaner (Credelio™) is the newest member of the novel isoxazoline chemical class to be developed to treat canine ectoparasitism. Administered orally, lotilaner is rapidly absorbed with peak blood levels occurring within 2 h post-treatment. A study was undertaken to determine the earliest onset of lotilaner’s efficacy against existing flea infestations.MethodsFrom 72 Beagles, 64 qualifying dogs were ranked in descending order of flea counts from a Day -8 infestation and placed into eight blocks. Within blocks, eight dogs were randomly allocated among eight groups: Groups 1 to 4 were treated orally with lotilaner, at as close as possible to the minimum dose rate of 20 mg/kg within 30 (± 5) minutes after feeding; Groups 5 to 8 were untreated controls. All dogs were infested with 100 ± 5 fleas on Day -2, and whole-body flea counts were completed at 30 min and one, two and 8 h after treatment. Efficacy calculations were based on arithmetic and geometric means if an adequate infestation (at least six of eight untreated dogs with a flea retention of ≥ 50%) was demonstrated in the equivalent control group.ResultsAdequate infestations were established in all control groups. At 30 min and 1 h post-treatment, relative to the matching untreated control group, there were no significant reductions in mean flea counts in lotilaner-treated dogs, although moribund fleas were evident at 1 h post-treatment. At 2 h after treatment, compared with the equivalent control group, the geometric mean flea count reduction in the lotilaner group was 64.0% (t (7) = 2.86, P = 0.0242). At 8 h after treatment, lotilaner efficacy was 99.6%. There were no treatment-related adverse events.ConclusionThis study demonstrates that lotilaner flavored chewable tablets are well tolerated and begin to kill fleas within 2 h of treatment, achieving 99.6% efficacy within 8 h. Lotilaner can therefore be used to quickly alleviate the flea irritation that arises from existing infestations.Electronic supplementary materialThe online version of this article (10.1186/s13071-017-2474-0) contains supplementary material, which is available to authorized users.

BackgroundEffective control of tick infestations on dogs is important to reduce the risk of transmission of bacterial, viral, and protozoal pathogens. Laboratory studies were initiated to determine the efficacy of lotilaner against common ticks infesting dogs in the United States.MethodsEight studies investigated the efficacy of lotilaner against ticks. In two studies dogs were infested with both Dermacentor variabilis and Rhipicephalus sanguineus: one additional study was completed for each of these species. Two studies assessed infestations with Amblyomma americanum and two with Ixodes scapularis. In all studies, dogs were ranked and blocked by counts from pre-treatment infestations and randomly allocated, at least eight per group, to be treated orally with lotilaner (minimum dose rate 20 mg/kg), or to be untreated controls. Treatments were administered on Day 0, within 30 min after dogs were fed. In all studies, infestations were performed with 50 adult ticks on Days -2, 7, 14, 21 and 28, and also on Day 35 for R. sanguineus, D. variabilis and I. scapularis. Tick counts were completed 48 h after treatment or after each subsequent challenge. An adequate infestation was defined as at least 25% of the infestation dose recovered from each of at least six control animals at each evaluation. Efficacy calculations for the primary objective were based on geometric means.ResultsIn all studies, lotilaner was 100% effective against existing infestations. For post-treatment assessments, on only two occasions did efficacy fall below 99%: in one D. variabilis study efficacy was 98.0% on Day 35 and in one I. scapularis study efficacy on Day 16 was 98.4%. Only mild and transient adverse events were observed, and none were considered to be related to treatment.ConclusionLotilaner was completely effective against existing infestations with four common species of ticks, D. variabilis, R. sanguineus, A. americanum and I. scapularis, that affect dogs in North America, with at least 4 weeks efficacy of 98.0% or more against subsequent challenge infestations. These results show that lotilaner is a highly effective isoxazoline that offers sustained efficacy against ticks through and beyond the one-month end-of-dose treatment interval.Electronic supplementary materialThe online version of this article (10.1186/s13071-017-2476-y) contains supplementary material, which is available to authorized users.

This paper discusses the problem of valuing the time spent on household production and presents estimates of that production for the United States in 1960 and 1970. The estimates are derived by using both opportunity cost and market cost valuations of household time. A comparative analysis of these estimates concludes first that opportunity cost estimates exceeded market cost estimates by 1.0 to 3.0 percent of the GNP. Second, the ratio of household production to the GNP, although declining slightly between 1960 and 1970, may in the long run tend to be relatively stable. These conclusions do not support the popular views that over time household production will decline in relative magnitude, or that the opportunity cost method of valuing household time, relative to the market cost method, is significantly upward biased.

No abstract