The effect of food on the disposition of radioactivity in rats after administration of 14C-haloperidol

Plasma, urine and faeces were assayed for total radioactivity after administration of 14C-haloperidol (0.6 mg/kg) to rats divided into three groups; intravenous, oral fasting and oral with food. Most urinary and faecal excretion of radioactivity occurred in the first 24 hours; by 5 days 96.5%, 81.5% and 62% of total 14C had been recovered from both routes for the intravenous, oral fasting and oral with food groups respectively. The fractionation pattern of urine radioactivity for all three groups was similar. Metabolite distribution did not change with time. Approximately 64% of the activity existed as amphoteric or non-ionised polar metabolites and 30% as substances which were benzene extractable from alkaline solution. Unchanged haloperidol was always less than 1% of total urine activity. An increase in peak level and a reduction in time to peak was seen in the plasma data for the oral with food group compared to the oral fasting group. This trend was confirmed and accentuated in a fourth group of rats trained to eat a large meal before drug administration. The apparent stimulatory effect of food on the rate and extent of absorption did not appear to be due to increased gastric emptying but could be related to the fat content in food. It is suggested that the lymphatics may play a part in haloperidol absorption in rats.