Antipyrine, erythromycin and oxytetracycline disposition in experimental fasciolosis

The effects of fasciolosis on drug disposition were studied by administration of antipyrine, erythromycin and oxytetracycline to sheep and cattle. Fasciolosis was produced by administration of 200 or 400 metacercariae (MC) of Fasciola hepatica to sheep and 500 MC to cattle. The disease was subsequently confirmed by determination of plasma glutamate dehydrogenase and gamma-glutamyl transferase and identification and quantitation of mature flukes in the liver at necropsy. Acute or subacute fasciolosis in sheep was accompanied by a significant decrease in the elimination rate constant (beta) and increase in the elimination half-time (t 1/2) for antipyrine and erythromycin when compared with controls or infected sheep which had been treated with the anthelmintic luxabendazole. An increase in apparent volume of distribution (Vd) was seen only for erythromycin in sheep given 400 MC. There were no changes in the disposition of oxytetracycline in sheep with either acute or subacute infection and no effects on disposition of the three test drugs in chronically infected sheep. With early chronic disease in calves, only the disposition of oxytetracycline was affected; not that of antipyrine or erythromycin.