Repeated oral administration of coumaphos in sheep: interactions of coumaphos with bishydroxycoumarin, trichlorfon, and phenobarbital sodium.

Interactions between treatments with coumaphos, bishydroxycoumarin (an anticoagulane), trichlorfon (an organophosphorous compound), and phenobarbital sodium (an inducer of microsomal enzymes) were investigated in sheep. A daily dose of 2 mg of coumaphos/kg of body weight for 6 days did not affect the plasma enzymes or the antiprothrombinemic effect of bishydroxy-coumarin in wethers. The treatment of ewes with an intravenous (IV) injection of trichlorfon, insufficient to produce significant inhibition of erythrocyte acetylcholinesterase (AChE) activity, appeared to produce additive effects with those produced by subsequent treatment with 4 mg of coumaphos/kg/day. In ewes given 40 mg of phenobarbital sodium/kg for 5 days intraperitoneally (IP), the anticholinesterase effect of 4 mg of coumaphos/kg was significantly reduced and signs of toxicity were not present. Treatment with daily doses of 2 mg of coumaphos/kg for 6 days did not modify the anticholinesterase effect of a 2nd series of treatments given 6 weeks later.