Autoradiographic and biochemical studies of drug distribution in the liver. I. [14C]Dehydrocorydaline

Whole body autoradiography revealed that the distribution pattern of [14C]dehydrocorydaline in the mouse and rat liver was heterogeneous (or reticular) regardless of time after intravenous administration of the labeled agent. Microautoradiography by dry-mounting method revealed that the macroscopic heterogeneous pattern was due to the periportal localization of the radioactive compound in the hepatic lobule. By comparison with [14C]salicylid acid, [14C]diphenylhydantoin and [14C]p-chlorophenoxyacetic acid whose distribution pattern are homogeneous in the liver, the present studies indicated that the existence and persistence of heterogeneous distribution of [14C]dehydrocorydaline in the liver had the following causes: 1. Shortly after intravenous administration, the amount of [14C]dehydrocorydaline circulated to the liver was greatly restricted by its significant distribution in non-hepatic tissues. This was shown by the whole body autoradiography, radiometry of tissues and quantitative comparison of volumes of distribution in non-hepatic tissues. Therefore, 2. perilobular hepatocytes alone could take up [14C]dehydrocorydaline and consequently, centrilobular cells were unavailable to it: heterogeneous distribution pattern is formed. This was shown by microautoradiography as described above, and by the rapid and significant uptake of [14C]dehydrocorydaline by isolated hepatocytes in vitro and by the liver to which the labeled agents were continuously administered in situ. It was also substantiated by the more homogeneous distribution pattern in the liver of the rat to which greater amount of [14C]dehydrocorydaline was gradually given into the portal vein and of the mouse with allyl formate-induced perilobular damage. 3. Redistribution of [14C]dehydrocorydaline scarcely occurred in the whole body and therefore radioactive substance was not significantly supplied to the liver: the distribution pattern remained unchanged. This was shown by the whole body autoradiography and radiometry of tissues.