Anthelmintic activity of the macrocyclic lactone F28249-α in sheep

W. L. Shoop From the Merck Institute for Therapeutic Research, PO Box 2000, Railway, NJ 07065-0900.

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J. R. Egerton From the Merck Institute for Therapeutic Research, PO Box 2000, Railway, NJ 07065-0900.

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C. H. Eary From the Merck Institute for Therapeutic Research, PO Box 2000, Railway, NJ 07065-0900.

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D. Suhayda From the Merck Institute for Therapeutic Research, PO Box 2000, Railway, NJ 07065-0900.

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SUMMARY

The macrolytic lactone F28249-α was titrated in experimentally infected sheep and found to be highly effective against most of the common gastrointestinal nematodes as a single oral dose, given at a rate of 0.025, 0.05, or 0.1 mg/kg. Specifically, maximal activity was evident at even the lowest dosage against adult Haemonchus contortus, Ostertagia circumcinta, Trichostrongylus axei, and T colubriformis and L4 O circumcinta. Activity against Oesophagostomum columbianum was also high at all dosages, with a calculated ed95 of 0.029 mg/kg. Cooperia curticei was eliminated at 0.1 mg/kg, but control was erratic at the lower dosages. The greatest weakness of this compound was its activity against C oncophora. The activity against this parasite was weak (≤ 85%) at all dosages, and the dosage-response curve was flat, suggesting dosages substantially higher than those given would be necessary for high-order control of this species.

SUMMARY

The macrolytic lactone F28249-α was titrated in experimentally infected sheep and found to be highly effective against most of the common gastrointestinal nematodes as a single oral dose, given at a rate of 0.025, 0.05, or 0.1 mg/kg. Specifically, maximal activity was evident at even the lowest dosage against adult Haemonchus contortus, Ostertagia circumcinta, Trichostrongylus axei, and T colubriformis and L4 O circumcinta. Activity against Oesophagostomum columbianum was also high at all dosages, with a calculated ed95 of 0.029 mg/kg. Cooperia curticei was eliminated at 0.1 mg/kg, but control was erratic at the lower dosages. The greatest weakness of this compound was its activity against C oncophora. The activity against this parasite was weak (≤ 85%) at all dosages, and the dosage-response curve was flat, suggesting dosages substantially higher than those given would be necessary for high-order control of this species.

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