FEED AND METHODS FOR CONTROLLING TICK INFESTATIONS IN A MAMMAL

Abstract

An oral animal feed and a method of controlling ticks in a mammal in need thereof by orally administering to the mammal an effective amount of a spinosyn for an effective time to thereby cause the amount of spinosyn in the mammal's blood to rise to and maintain at a therapeutically effective level for controlling ticks.

Claims

1. A method of controlling a tick infestation in a mammal in need thereof, comprising orally administering to said mammal an effective amount of a spinosyn for an effective time at a frequency of at least 4 times per month.

2. The method of claim 1, wherein said mammal is selected from the group consisting of: a wild animal; a farm animal; a companion animal; and a canine.

3. The method claim 1, wherein said spinosyn is spinosad.

4. The method of claim 1, wherein said spinosyn is provided in a feed selected from the group consisting of a dry food and a wet food.

5. The method of claim 1, wherein said spinosyn is present in an amount of between about 0.005% to 2% of a feed.

6. The method of claim 1, wherein said spinosyn is administered to said mammal in an amount of between about 0.625 mg/kg and 10 mg/kg of weight of said mammal.

7. The method of claim 1, wherein said frequency is selected from the group consisting of at least 3 times per week, substantially daily and daily.

8. The method of claim 1, wherein said effective time is selected from the group consisting of at least one week and at least two weeks.

9. The method of claim 1, wherein said administration provides a therapeutically effective level of spinosyn in said mammal's blood within a time period selected from the group consisting of one week of the first administration of said spinosyn and two days of the first administration of said spinosyn.

10. The method of claim 1, wherein said administration provides a therapeutically effective level of spinosyn in said mammal's blood for a time period selected from the group consisting of at least 30 days, at least 60 days, at least 90 days, at least 180 days and at least 365 days.

11. The method of claim 1, wherein said administration provides a concentration of spinosyn of in the mammal's blood selected from the group consisting of: more than about 300 ng/mL and less than about 6000 ng/mL in said mammal's blood for at least 30 days; more than about 300 ng/mL and less than about 2500 ng/mL; more than about 300 ng/mL and less than about 2000 ng/mL; and more than about 400 ng/mL and less than about 1500 ng/mL in said mammal's blood for at least 30 days.

12. The method of claim 11, wherein said administration provides a concentration of spinosyn of more than about 300 ng/mL and less than about 6000 ng/mL in said mammal's blood for a period of time selected from the group consisting of at least 30 days and at least 365 days.

13. The method of claim 1, wherein said spinosyn is administered for a number of days selected from the group consisting of at least 15 out of 30 days and at least 20 out of 30 days.

14. The method of claim 1, wherein said spinosyn is provided as a component of a feed that comprises one or more other active substances.

15. The method of claim 1, further comprising discontinuing the administration of spinosyn for a period of time selected from the group consisting of at least 3 days and at least 7 days, wherein the mammal's blood concentration of spinosyn is maintained at a therapeutically effective level during the period of time.

16. The method of claim 15, further comprising resuming the administration of spinosyn after the discontinuing of the administration of spinosyn and thereby continuing to maintain the mammal's blood concentration of spinosyn at the therapeutically effective level.

17. The method of claim 1, wherein the oral administration includes a feeding frequency selected from the group consisting of at least 3 times per week, substantially daily and daily.

18. A feed or a chew for a mammal, comprising a feed selected from the group consisting of: a chew, a dry feed and a wet feed; and at least one spinosyn.

19. The feed or a chew of claim 18, wherein said spinosyn is present in an amount of between about 0.005 wt. % to 2 wt. % of the feed or the chew.

20. The feed or the chew of claim 18, wherein said spinosyn in the feed or the chew is administered to said mammal in an amount of between about 0.625 mg/kg and 10 mg/kg of weight of said mammal.

21. The feed or the chew of claim 18, wherein said spinosyn is spinosad.

Description

BRIEF DESCRIPTION OF THE FIGURES

[0030] FIG. 1. A graph of the Arithmetic Mean Efficacy, Percent Efficacy=[AM ticks CONTROLAM ticks TREATED]/AM ticks CONTROL, measured at 14, 21, 30, 37, 44, 51, and 58 days after treatment with spinosad.

[0031] FIG. 2. A graph of the Average Plasma Levels of Spinosad. In units of ng of spinosad per ml of plasma measured over time (in units of hours after dosing). Values determined for animals treated with either 2.5-5.0 mg of spinosad/kg of animal body mass/day (circles) or a once monthly dose (squares). For animals given a daily dose of spinosad, the dose of spinosad was increased from 2.5 mg/kg/day to 5.0 mg/kg/day of spinosad at about 700 hours.

DESCRIPTION

[0032] All ratios, percentages, and parts discussed herein are by weight unless otherwise specified.

[0033] The term controlling a tick infestation refers to preventing, treating, minimizing or eliminating an infestation by ticks on a mammal.

[0034] The term tick refers to any member of the order Ixodida. The term tick includes the egg, larval, nymph, and adult stages of development. More particularly, the term tick includes ticks of the families Ixodidae and Argasidae. More particularly, the term tick includes species of the genera Africaniella, Amblyomma, Anomalohimalaya, Bothriocroton, Dermacentor, Haemaphysalis, Hyalomma, Ixodes, Margaropus, Nosomma, Rhipicentor, Rhipicephalus, Antricola, Argas, Nothoaspis, Ornithodoros, and Otobius.

[0035] The term mammal refers to any member of the class Mammalia. In particular, it may refer to wild mammals, such as wolves, coyotes, jackals, deer, elk, moose, reindeer, and the like. It may also refer to farm animals, such as cows, sheep, pigs, bison, horses and the like. It may also refer to companion animals. It may also refer to humans.

[0036] The term companion animal refers to any domestic animal that may be kept as a pet. This includes, but is not limited to, horses, dogs, wolves, coyotes, cats, hamsters, gerbils, mice, guinea pigs, ferrets, rabbits, etc.

[0037] The term canine refers to any member of the genus Canis, which includes such species as wolves, dogs, coyotes and jackals.

[0038] The term feline refers to any member of the subfamily Felidae, which includes such species as the domestic cat, bobcats, wildcats, ocelots, members of the genus lynx, Pallas's cat and cougars.

[0039] In carrying out the methods of this disclosure, a feed is an animal feed, snack, treat or other supplemental feed that may be administered daily or substantially daily. By using different forms of feed, e.g., kibble and treats or chews, the mammal's meals and snacks may be varied from time to time while still conveniently administering a daily dose of spinosyn.

[0040] The term chew refers to a treat that has flavor and aromatic properties that are appealing to a canine, but typically has no nutritional value. In carrying out the methods of this disclosure, a feed and/or a chew may be used interchangeably.

[0041] The term effective time, also referred to herein as effective duration, for the purposes of this disclosure includes at least the duration of feed administration needed to bring the level of spinosyn in the mammal's blood to a sufficiently high level for controlling ticks, i.e., a therapeutically effective level. In some embodiments, the effective time may be as little as three days. In other instances, the effective time may be seven days or fifteen days or longer. As discussed below, the effective time will vary based on how frequently the feed or spinosyn is administered.

[0042] As just alluded, the effective time will vary as a function of the frequency at which the feed is administered. The term effective frequency as used herein means the number of feedings over a given time that produce a therapeutically effective concentration of spinosyn in the mammal's blood. In all events, the term effective frequency as used herein contemplates multiple feedings including the spinosyn per month. One of skill in the art will appreciate that the feed may be administered in a range of frequencies. For example, the spinosyn may be administered at a frequency of daily, every other day, every third day, once per week or even at inconsistent time intervals.

[0043] Further, as discussed above, the effective frequency may affect the duration required to obtain a therapeutically effective level of spinosyn in the mammal's blood. By way of example, if the mammal were being fed the feed composition daily, the duration of feed administration required to achieve a therapeutically effective level of spinosyn in the mammal's blood, and thus the effective time, would be comparatively less than if the mammal were being fed the feed composition only once or twice per week.

[0044] Further, the effective frequency is influenced by the amount of the daily dose in mg/kg of body weight of the mammal. Particularly, at slightly higher daily doses, e.g., greater than 1.0 mg/kg, missed doses have less of an impact on efficacy.

[0045] Further, the effective frequency is influenced by the duration of treatment. In the initial stages, i.e., before the amount of spinosyn in the mammal's blood has reached a therapeutically effective level, the animal feed may need to be administered at a greater frequency than would be necessary if it were being administered after a longer period of use, i.e., once a therapeutically effective level is obtained.

[0046] For purposes of this disclosure, substantially daily means a sufficiently regular basis such that the spinosyn concentration in the mammal's blood rises to and remains at a therapeutically effective level. For example, the disclosed feed composition can preferably be fed to a mammal every day indefinitely. However, as a practical matter, there are many reasons days may be missed or skipped periodically. For example, the mammal may be ill or the owner may run out of the feed composition. The disclosed method is robust enough that the mammal will still be protected from ticks to some extent even with occasional interruptions in doses of spinosyn. In carrying out the method of this disclosure, the term substantially daily includes at least 10 days per month, more preferably at least 15 days per month, still more preferably at least 20 days per month. All of these feeding frequencies, whether they be, e.g., three times per week, every other day or daily, fit under the umbrella of substantially daily as used in this disclosure, provided that they promote the spinosyn reaching and maintaining a therapeutically effective level of the spinosyn in the mammal's blood.

[0047] The term therapeutically effective means that the dose of a spinosyn in the feed or concentration of a spinosyn in the blood is sufficient to control the tick infestation better than if no drug were present. The spinosyn may be present in, e.g., the feed, or the mammal's blood on its own or with one or more additional active substances. Preferably it controls the tick infestation at around at least 50% better than if no drug were present, and more preferably it controls the tick infestation at about at least 90% better than if no drug were present.

[0048] In carrying out the methods of this disclosure, an effective or therapeutically effective amount of a spinosyn is administered orally to the mammal. The term effective amount or therapeutically effective amount refers to the amount needed to control the tick infestation. As those in the art will understand, this amount will vary depending upon a number of factors. These factors include, for example, the type of mammal being treated, its body weight and general physical condition.

[0049] While this disclosure describes concentrations of spinosyn in terms of feeds such as kibble, it also contemplates administration using other dosage forms, such as treats or chews. It is also contemplated that the spinosyn may be administered by itself or in a tablet, liquid, gel or other suitable form for oral administration. One of skill in the art will appreciate that the concentration of spinosyn will vary according to the particular dosage form. For example, where the dosage form is a treat or chew, the concentration of spinosyn in the treat or chew will be greater than, e.g., the concentration of spinosyn in kibble. For example, if the daily dose of spinosyn based on the weight of the canine is 10 mg, then a typical 5 g treat or chew would contain about 0.2 percent spinosyn (by weight). Since the amount of kibble consumed in a day is more than 5 g, the percent spinosyn in kibble will be smaller.

[0050] In general, an effective amount refers to a dose of from about 0.625 to about 10 mg of the spinosyn/kg of body weight of the mammal. More preferably, an effective amount refers to a dose of from about 1 to about 4.5 mg of the spinosyn/kg of body weight of the mammal. More commonly, the effective amount is from about 1 to about 3.75 mg/kg of body weight of the mammal.

[0051] Animal feeds will typically contain from about 0.005 to about 2 percent of spinosyn (by weight) in the feed, preferably between about 0.01 to about 0.5 percent of spinosyn (by weight) in the feed, most preferably between about 0.03 to about 0.2 percent of spinosyn (by weight) in the feed.

[0052] In one aspect, this disclosure relates to a method of controlling a tick infestation in a mammal by administering a systemically active oral composition including spinosyn, or a physiologically acceptable derivative or salt thereof, and animal feed at least once per week, more preferably three times per week, most preferably substantially daily.

[0053] In another aspect, this disclosure relates to a systemically active oral composition that includes a spinosyn and animal feed.

[0054] This disclosure also relates to the use of a spinosyn for the manufacture of an animal feed for controlling a tick infestation on a mammal.

[0055] This disclosure also relates to a method of controlling a tick infestation on a mammal for a prolonged time, comprising orally administering daily or substantially daily doses of an effective amount of a spinosyn to the mammal in, e.g., a feed. A daily feed is a feed which is intended to be administered daily, however which may be administered less frequently than daily, as described herein. This method is especially useful for controlling ticks on a mammal for a prolonged time comprising orally administering substantially daily doses of an effective amount of a spinosyn to the mammal.

[0056] An aspect of this disclosure is the oral administration of an amount of spinosyn that is, in and of itself, ineffective or sub-optimal for controlling a tick infestation in a mammal in a single dose, e.g., once every month, but over time with repeated administrations, as described herein, results in efficacious control of tick infestations. Ineffective or sub-optimal means that a single dosing, as well as several dosings, results in less than a 50% reduction in the tick infestation, including no, or substantially no, reduction, as compared to no drug administration at all. This reflects the chronic, rather than acute, administration aspect disclosed herein.

[0057] Embodiment 1: A method of controlling a tick infestation in a mammal in need thereof, comprising orally administering to said mammal an effective amount of a spinosyn for an effective time at a frequency of at least 4 times per month.

[0058] Embodiment 2: The method of embodiment 1, wherein said mammal is selected from the group consisting of a wild animal, a farm animal, a companion animal and a canine.

[0059] Embodiment 3: The method of embodiments 1 or 2, wherein said spinosyn is spinosad.

[0060] Embodiment 4: The method of any of embodiments 1-3, wherein said is provided in a feed selected from the group consisting of dry food and a wet food.

[0061] Embodiment 5: The method of any of embodiments 1-3, wherein said spinosyn is present in an amount of between about 0.005% to 2% of a feed.

[0062] Embodiment 6: The method of any of embodiments 1-5, wherein said spinosyn is administered to said mammal in an amount of between about 0.625 mg/kg and 10 mg/kg of weight of said mammal.

[0063] Embodiment 7: The method of any of embodiments 1-6, wherein said frequency is selected from the group consisting of at least 3 times per week, substantially daily and daily.

[0064] Embodiment 8: The method of any of embodiments 1-7, wherein said effective time is selected from the group consisting of at least one week and at least two weeks.

[0065] Embodiment 9: The method of any of embodiments 1-8, wherein said administration provides a therapeutically effective level of spinosyn in said mammal's blood within a time period selected from the group consisting of one week of the first administration of said spinosyn and two days of the first administration of said spinosyn.

[0066] Embodiment 10: The method of any of embodiments 1-9, wherein said administration provides a therapeutically effective level of spinosyn in said mammal's blood for a time period selected from the group consisting of at least 30 days, at least 60 days, at least 90 days, at least 180 days and at least 365 days.

[0067] Embodiment 11: The method of any of embodiments 1-10, wherein said administration provides a concentration of spinosyn of more than about 300 ng/mL and less than about 6000 ng/mL in said mammal's blood for a period of time selected from the group consisting of at least 30 days and at least 365 days.

[0068] Embodiment 12: The method of any of embodiments 1-11, wherein said spinosyn is administered for a number of days selected from the group consisting of at least 15 out of 30 days and at least 20 out of 30 days.

[0069] Embodiment 13: The method of any of embodiments 1-12, wherein said spinosyn is provided as a component of a feed that comprises one or more other active substances.

[0070] Embodiment 14: The method of any of embodiments 1-13, further comprising discontinuing the administration of spinosyn for a period of time selected from the group consisting of at least 3 days and at least 7 days, wherein the mammal's blood concentration of spinosyn is maintained at a therapeutically effective level during the period of time.

[0071] Embodiment 15: The method of embodiment 14, further comprising resuming the administration spinosyn after the discontinuing of the administration of spinosyn and thereby continuing to maintain the mammal's blood concentration of spinosyn at the therapeutically effective level.

[0072] Embodiment 16: The method of embodiment 1, wherein the spinosyn is a component of a chew.

[0073] Embodiment 17: The method of embodiment 16, wherein the oral administration includes a feeding frequency selected from the group consisting of: at least 3 times per week, substantially daily and daily.

[0074] Embodiment 18: A spinosyn for use in controlling ticks on a mammal in need thereof, said spinosyn being administered in an effective amount to said mammal for an effective time at a frequency of at least four times per month.

[0075] Embodiment 19: The spinosyn of embodiment 18, wherein said mammal is selected from the group consisting of a wild animal, a farm animal, a companion animal and a canine.

[0076] Embodiment 20: The spinosyn of any of embodiments 18-19, wherein said spinosyn is spinosad.

[0077] Embodiment 21: The spinosyn of any of embodiments 18-20, wherein said wherein said spinosyn is provided in a feed selected from the group consisting of dry food and wet food.

[0078] Embodiment 22: The spinosyn of any of embodiments 18-21, wherein said spinosyn is present in an amount of between about 0.005% to 2% of feed.

[0079] Embodiment 23: The spinosyn of any of embodiments 18-22, wherein said spinosyn is administered to said mammal in an amount of between about 0.625 mg/kg and 10 mg/kg of weight of said mammal.

[0080] Embodiment 24: The spinosyn of any of embodiments 18-23, wherein said administering includes a feeding frequency selected from the group consisting of at least 3 times per week, substantially daily and daily.

[0081] Embodiment 25: The spinosyn of any of embodiments 18-24, wherein said effective time is selected from the group consisting of at least one week and at least two weeks.

[0082] Embodiment 26: The spinosyn of any of embodiments 18-25, wherein said administration provides a therapeutically effective level of spinosyn in said mammal's blood within a period of time selected from the group consisting of one week of the first administration of said spinosyn and two days of the first administration of said spinosyn.

[0083] Embodiment 27: The spinosyn of any of embodiments 18-26, wherein said administration provides a therapeutically effective level of spinosyn in said mammal's blood for a period of time selected from the group consisting of at least 30 days, at least 60 days, at least 90 days, at least 180 days and at least 365 days.

[0084] Embodiment 28: The spinosyn of any of embodiments 18-27, wherein said administration provides a concentration of spinosyn of more than about 300 ng/mL and less than about 6000 ng/mL in said mammal's blood for a period of time selected from the group consisting of at least 30 days and at least 365 days.

[0085] Embodiment 29: The spinosyn of any of embodiments 18-28, wherein said feed is administered for a number of days out of 30 selected from the group consisting of at least 15 days and at least 20 days.

[0086] Embodiment 30: The spinosyn of any of embodiments 18-29, wherein the spinosyn is a component of a feed that comprises one or more additional active substances.

[0087] Embodiment 31: The spinosyn of any of embodiments 18-30, further comprising discontinuing the administration of spinosyn for a period of time selected from the group consisting of at least 3 days and at least 7 days, wherein the mammal's blood concentration of spinosyn is maintained at a therapeutically effective level.

[0088] Embodiment 32: The spinosyn of embodiment 31, further comprising resuming the administration of spinosyn after the discontinuing of the administration of spinosyn and thereby maintaining the mammal's blood concentration of spinosyn at the therapeutically effective level.

[0089] Embodiment 33: The spinosyn of embodiments 18-32, wherein the spinosyn is a component of a chew.

[0090] Embodiment 34: The spinosyn of embodiment 33, wherein the administration includes a feeding frequency selected from the group consisting of: at least 3 times per week, substantially daily and daily.

[0091] Embodiment 35: A feed or chew for controlling ticks in a mammal, comprising an effective amount of a spinosyn to control a tick infestation when administered for an effective time at a frequency of at least four times per month.

[0092] Embodiment 36: The feed or chew of embodiment 35, wherein said mammal is selected from the group consisting of a wild animal, a farm animal, a companion animal and a canine.

[0093] Embodiment 37: The feed or chew of any of embodiments 35-36, wherein said spinosyn is spinosad.

[0094] Embodiment 38: The feed or chew of any of embodiments 35-37, wherein said feed or chew is a feed selected from the group consisting of a dry food and a wet food.

[0095] Embodiment 39: The feed or chew of any of embodiments 35-38, wherein said spinosyn is present in an amount of between about 0.005% to 2% of a feed.

[0096] Embodiment 40: The feed or chew of any of embodiments 35-39, wherein said spinosyn is administered to said mammal in an amount of between about 0.625 mg/kg and 10 mg/kg of weight of said mammal.

[0097] Embodiment 41: The feed or chew of any of embodiments 35-40, wherein said administration includes a feeding frequency selected from the group consisting of at least 3 times per week, substantially daily and daily.

[0098] Embodiment 42: The feed or chew of any of embodiments 35-41, wherein said effective time comprises administering the feed or chew for a period of time selected from the group consisting of at least one week and at least two weeks.

[0099] Embodiment 43: The feed or chew of any of embodiments 35-42, wherein said administration provides a therapeutically effective level of spinosyn in said mammal's blood within a time period selected from the group consisting of one week of the first administration of said feed or chew and two days of the first administration of said feed or chew.

[0100] Embodiment 44: The feed or chew of any of embodiments 35-43, wherein said administration provides a therapeutically effective level of spinosyn in said mammal's blood for a time period selected from the group consisting of at least 30 days, at least 60 days, at least 90 days, at least 180 days and at least 365 days.

[0101] Embodiment 45: The feed or chew of any of embodiments 35-44, wherein said administration provides a concentration of spinosyn of more than about 300 ng/mL and less than about 6000 ng/mL in said mammal's blood for a period of time selected from the group consisting of at least 30 days and at least 365 days.

[0102] Embodiment 46: The feed or chew of any of embodiments 35-45, wherein said feed or chew is administered for a number of days out of 30 selected from the group consisting of at least 15 days and at least 20 days.

[0103] Embodiment 47: The feed or chew of any of embodiments 35-46, wherein said feed or chew comprises one or more other active substances.

[0104] Embodiment 48: The feed or chew of any of embodiments 35-47, further comprising discontinuing the administration of the feed or chew for a period of time selected from the group consisting of at least 3 days and at least 7 days, wherein the mammal's blood concentration of spinosyn is maintained at a therapeutically effective level.

[0105] Embodiment 49: The feed or chew of embodiment 48, further comprising resuming the administration of feed or chew after the discontinuing of the administration of feed or chew and thereby maintaining the mammal's blood concentration of spinosyn at the therapeutically effective level.

[0106] In an aspect of any of the embodiments, administration provides a concentration of spinosyn of more than about 300 ng/mL and less than about 6000 ng/mL in said mammal's blood for at least 30 days. More preferably, administration provides a concentration of spinosyn of more than about 300 ng/mL and less than about 2500 ng/mL in said mammal's blood for at least 30 days. Still more preferably, administration provides a concentration of spinosyn of more than about 300 ng/mL and less than about 2000 ng/mL in said mammal's blood for at least 30 days. Still more preferably, administration provides a concentration of spinosyn of more than about 400 ng/mL and less than about 1500 ng/mL in said mammal's blood for at least 30 days.

[0107] In an aspect of any of the embodiments, administration provides a concentration of spinosyn of more than about 300 ng/mL and less than about 6000 ng/mL in said mammal's blood for at least 365 days. More preferably, administration provides a concentration of spinosyn of more than about 300 ng/mL and less than about 2500 ng/mL in said mammal's blood for at least 365 days. Still more preferably, administration provides a concentration of spinosyn of more than about 300 ng/mL and less than about 2000 ng/mL in said mammal's blood for at least 365 days. Still more preferably, administration provides a concentration of spinosyn of more than about 400 ng/mL and less than about 1500 ng/mL in said mammal's blood for at least 365 days.

EXAMPLES

[0108] The following examples illustrate the methods of this disclosure:

Example 1

[0109] Efficacy of Spinosyn Administered per os, i.e. by Mouth, to Dogs for the Treatment and Control of Rhipicephalus sanguineus.

[0110] Methods: A pool of 40 dogs are to be screened before inclusion in this example by preliminarily infesting them with 100 unfed adult Ctenocephalidesfelis in order to produce a pool of dogs that can suitably sustain a reliable infestation rate of approximately 50% of live fleas over a 48-hour period. The dogs with the highest live flea counts are to be randomly allocated to 2 treatment groups (6 dogs per group) based on their pre-treatment flea counts from experimental infestations. The first treatment group is to be the control group and the second treatment group to be the test group.

[0111] The dogs are to be housed individually during the study period and are to be fed a commercial dry dog food ration with ad libitum access to water.

[0112] Each dog in the test group is to receive by mouth a liquid formulation of spinosyn preferably spinosad. The dosage of 2.5 mg/kg of the dog's weight is to be administered to the dogs on each of days 0-29 and the dosage of 5 mg/kg of the dog's weight is to be administered on days 30-50.

[0113] Dogs in the control group are not to receive spinosyn or any other tick control treatment. Each dog in the test group is to be offered its daily ration (dry food) and the individual doses of liquid formulation are to be administered after the individual dog has eaten at least 25% of its total daily ration. After receiving the dose of spinosyn the dogs are to be allowed to continue eating. This mimics incorporating the spinosyn in feed. Each dog in the test group and the control group is to be experimentally infested with 50 unfed adult ticks (ca. 50% male/50% female) on test days 12, 19, 28, 35, 42, 49 and 56. Comb counts for attached live and moribund adult ticks are to be conducted on days 14, 21, 30, 37, 44, 51 and 58. Note that the dosage is to be increased at day 30 and the final dose is to be given on day 50.

[0114] Results: Referring now to FIG. 1. Percent reduction in attached live and moribund adult tick counts for the test group treated with spinosad as compared to the control group is shown in the graph. Percent Efficacy is determined according to the formula [AM ticks CONTROLAM ticks TREATED]/AM ticks Control. This is plotted versus time in days after initial treatment. As can be seen in FIG. 1, the daily dose is increased from 2.5 mg/kg/day to 5.0 mg/kg/day at about hour 700 (around day 30). The corresponding increase in efficacy is clear from the efficacy in days 37-50. The efficacy at day 58 is after the about 8 day wash-out period following the last dose on day 50.

[0115] Using the same study method as described above, blood is to be drawn at 72, 120, 168, 336, 504, 720 and 888 hours after the initial dose of spinosyn is administered. The average concentration of spinosyn in the blood for different dosage levels can then be determined.

[0116] Referring now to TABLE 1 and FIG. 2. Sample results are shown for the average plasma concentration of spinosad in a canine's blood (ng/mL) versus time in hours for different dosage levels of spinosad. By way of comparison, the average plasma concentration of spinosyn for a single-dose administration to be given monthly (squares) is shown with the average plasma concentration of spinosyn for a substantially daily dose of 2.5 mg/kg/day or 5.0 mg/kg/day (circles). The daily dose is increased from 2.5 mg/kg/day to 5.0 mg/kg/day at about hour 700 (around day 30).

TABLE-US-00001 TABLE 1 Average Plasma Concentration (ng/mL) - Spinosad 2.5-5.0 mg/kg/day Monthly Hours spinosad Dose 1 No Data 585.43 2 1119.50 4 1830.25 8 2730.50 12 3592.50 24 1594.50 72 221.50 359.48 120 327.07 320.25 168 455.78 265.10 336 566.25 128.95 504 668.77 69.78 720 533.12 32.23 888 635.72 20.44 1056 967.33 No Data 1224 1172.60 1392 761.45

[0117] While this invention has been described as having an exemplary design, the present invention may be further modified within the spirit and scope of this disclosure. This application is therefore intended to cover any variations, uses, or adaptations of the invention using its general principles.