Autoradiographic and biochemical studies of drug distribution in the liver II. [35S] chlorpromazine and [14C] imipramine

Autor: Hisashi Miyazaki, Toshihiko Fujii, Masahisa Hashimoto, Keiko Nambu, Katashi Matsumoto
Rok vydání: 1984
Předmět:
Zdroj: European Journal of Drug Metabolism and Pharmacokinetics. 9:247-255
ISSN: 2107-0180
0378-7966
DOI: 10.1007/bf03189648
Popis: Whole body autoradiography revealed that the distribution pattern of [35S]chlorpromazine and [14C]imipramine in the mouse and rat liver was heterogeneous (or reticular) shortly after intravenous administration of the labeled agents and then became homogeneous. Microautoradiography by dry-mounting method revealed that the macroscopic heterogeneous pattern of [35S]chlorpromazine was due to its periportal localization in the hepatic lobule. The present studies indicated that the heterogeneous distribution was re-arranged to a homogeneous one in the following way: 1. The amount of [35S]chlorpromazine and [14C]imipramine circulated to the liver was greatly restricted by their significant distribution in non-hepatic tissues shortly after administration. This was shown by whole body autoradiography, radiometry of tissues and volumes of distribution in non-hepatic tissues. Therefore, 2. perilobular hepatocytes alone could take up the agents and consequently, centrilobular cells were unavailable to them: heterogeneous distribution pattern is formed. This was shown by microautoradiography described above, and by the rapid and significant uptake of the agents by isolated hepatocytes in vitro and of [35S]chlorpromazine by the liver to which the agent was continuously administered in situ. However, 3. re-distribution of [35S]chlorpromazine and [14C]imipramine occurred thereafter. Therefore, the radioactive compounds were significantly supplied to the liver late after administration: the pattern became homogeneous. This was shown by the whole body autoradiography and radiometry.
Databáze: OpenAIRE
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