Estimation of allantoin flux using continuous infusion of [14C]allantoin: Sensitivity to plasma loading with unlabelled allantoin

Allantoin net flux through the plasma allantoin compartment was determined in sheep given a roughage diet by means of a continuous infusion of [4,5-14C]allantoin for 17 h. Unlabelled allantoin was infused intravenously during the last 7 h of the tracer infusion to increase the allantoin flux by approximately 75%. When unlabelled allantoin was infused, the specific radioactivity of allantoin in plasma and urine declined exponentially to approach a lower plateausome 2–3 h later. The estimate of net flux during the infusion of unlabelled allantoin, estimated from blood plasma and urine, was on average 79 and 90% of expected values. Expected values of allantoin net flux during infusion of unlabelled allantoin were calculated as the sum of allantoin net flux pre-loading plus the known rate of infusion of the allantoin load. It is probable that endogenous allantoin synthesis was decreased by the infusion of allantoin: allosteric inhibition of uricase appears a plausible explanation for this observation, and for lower estimates of net flux. Appearance of labelled allantoin-C in ruminal or blood bicarbonate was negligible. Our results indicate that net flux of allantoin through blood plasma is a good predictor of the entry rate of allantoin into the primary compartment and should be a better predictor of rumen microbialoutflow than urinary allantoin excretion. However, measurements of allantoin-specific radioactivity, during continuous infusion, should be taken after a period of 24 h, at which time the true plateau specific radioactivity value of allantoin in plasma would be attained.