In vivo anthelmintic activity of Phytolacca icosandra against Haemonchus contortus in goats

Two separate controlled and blinded studies were conducted to confirm the dose and non-interference of spinosad and milbemycin oxime (MO) administered orally in combination or alone to dogs for the treatment and control of experimentally induced flea infestations (Ctenocephalides felis) and adult hookworm infections (Ancylostoma caninum). For each study, dogs were allocated randomly based on pre-treatment adult flea and hookworm egg counts to one of four treatment groups of 10 animals each. In each study, spinosad and MO in combination, using the lower half (30-45 mg/kg spinosad; 0.5-0.75 mg/kg MO) of the US commercial dose band (30-60 mg/kg spinosad; 0.5-1.0mg/kg MO) of each active ingredient, or individually alone using the full dose range, were given orally to dogs on Day 0 using a tablet formulation. A placebo control was treated similarly. In one study, on Days -1, 5, 12, 19, 28 and 35 each dog was infested with approximately 100 unfed adult C. felis obtained from the investigator's established flea colony. All dogs were infested via the same method. Forty-eight hour post-infestation flea comb counts were conducted on Days 1, 7, 14, 21, 30 and 37 and were used to determine the knockdown and residual flea activity. In the second study, on Day -27 each of 48 dogs were experimentally inoculated with 100 third-stage infective larvae of the hookworm, A. caninum. Dogs were treated on Day 0 and necropsied on Day 7 or Day 8. All nematodes in the intestinal tract were collected on Day 7 or Day 8, identified and counted by species and stage. Post-treatment, the geometric mean live flea counts were significantly different (p-value<0.0001) between the spinosad/MO combination and the spinosad only treatment groups as compared to the vehicle control group. The flea counts in the MO only group and the control group were not statistically different. The spinosad and MO combination group and the spinosad only treatment group demonstrated significantly different knockdown (100%) and post-treatment residual flea efficacy at Day 30 was 100% for both groups as compared to the vehicle control. The presence of MO in combination with spinosad did not interfere with the flea efficacy of spinosad as compared to the spinosad only group. MO alone did not demonstrate any flea efficacy. Post-treatment, the geometric mean A. caninum worm counts were significantly different (p-value<0.0001) between the spinosad and MO combination group as compared to the vehicle control group. The worm counts in the MO only group and the combination group were not statistically different. The spinosad and MO combination group (99.8% reduction) and the MO only treatment group (99.5% reduction) both demonstrated significantly different hookworm efficacy as compared to the vehicle control group. The presence of spinosad in combination with MO did not interfere with the hookworm efficacy of MO as compared to the MO only group. Spinosad alone did not demonstrate any hookworm efficacy. In summary, flavored spinosad and MO combination tablets administered orally to dogs at the lower end (30-45 mg/kg spinosad; 0.5-0.75 mg/kg MO) of the US commercial tablet unit dose range (30-60 mg/kg spinosad; 0.5-1.0mg/kg MO) were both safe and highly efficacious delivering 100% knockdown and 30 days of residual adult flea control on experimentally infested dogs as well as >99% adult hookworm efficacy evaluated under laboratory conditions. Interference between either drugs was not demonstrated for both of these dose limiting parasites.