The kidney is the main site of interferon catabolism

The fate of human natural interferons alpha and beta and of recombinant (R) alpha 2 has been investigated by using an isolated and perfused rabbit kidney preparation with a normal physiological performance. A remarkable amount of IFN is filtrated in a monoexponential fashion, reabsorbed and very likely degraded in tubular cells with negligible excretion in the urine. The disappearance rate of HuRIFN-alpha 2 is higher than natural HuIFNs-alpha and beta and is in keeping with the lower molecular weight of RIFN-alpha 2. Differences in molecular charge or shape are probably responsible for the slightly reduced filtration of IFN-beta. Pharmacokinetic studies in animal models appear instructive and useful for devising improved dosage schedules in clinical trials.