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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.

Rapid intravenous administration (60 mg s-1) of chloramphenicol (50 mg kg-1) in a 40 per cent w/v polyethylene glycol (400 to 600), 30 per cent ethyl alcohol, 2 per cent benzyl alcohol and 28 per cent distilled water vehicle produced a transient but significant decrease in systemic arterial blood pressure and heart rate with no effect on central venous pressure in sodium pentobarbital anaesthetised dogs. The vehicle alone had no significant effect on any of the parameters studied. Various approaches including the use of anticholinergic, antihistaminergic, antiadrenergic and ganglion blocking drugs failed to attenuate chloramphenicol induced hypotension and bradycardia. However, the hypertensive response to bilateral carotid arterial occlusion was significantly attenuated by rapid intravenous administration of chloramphenicol. The results clearly indicate that chloramphenicol itself, but not its vehicle, is responsible for the severe hypotension and bradycardia. These results also suggest that chloramphenicol-induced hypotension and bradycardia might be mediated peripherally via vasodilation due to its direct effect on vascular smooth muscle and centrally via interruption of the baroreceptor reflex pathway.

Chloramphenicol was administered intravenously for eight to 17 days to five newborn calves at a daily dosage of 100 mg kg-1. Haemodynamic, haematological, blood chemistry, serum enzyme, urinalysis and clinical responses were evaluated. High levels of serum chloramphenicol were observed throughout the study although a marked increase in elimination rate was seen with increasing age. The most severe adverse effects were severe hypotension following rapid intravenous administration and severe gastrointestinal dysfunction with diarrhoea accompanying prolonged high dosage. There appeared to have been a haematological effect in one calf, but it was of minor significance compared with the other effects.