Whole body autoradiographic studies on the distribution of 3H-labeled penfluridol (3H-TLP-607) in mice and rats.

Sato, Yoshishige; Sakuma, Mari; Kimura, Makiko; Nakazato, Fumie; Naito, Kunihiko; Otsuka, Minezo

doi:10.1248/cpb.22.1996

Cited by 3 publications

(2 citation statements)

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“…Such heterogeneous distribution pattern in the liver has been occasionally observed by autoradiography for labeled chloropromazine (5), irnipraSend reprint requests to: T. Fujii, Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Enoki 33-94, Suita, Osaka, 564 Japan. mine (6), aminotriazole (7), chloroform (8), hexachlorobinephyl (9) and others (10)(11)(12)(13)(14). The pattern is rather rare since, in general, radioactive compounds are distributed relatively evenly in the liver.…”

Section: Introductionmentioning

confidence: 99%

“…The heterogeneous distribution patterns in the liver were found to be classified into three according to its change following time after administration of radioactive substances: firstly, heterogeneous distribution regardless of time (e.g., dehydrocorydaline) (1,14), secondly, change from heterogeneous to homogeneous distribution (5,6,(10)(11)(12)(13) and lastly, change from homogeneous to heterogeneous distribution (7)(8)(9). These facts suggest that characterization of histological features and elucidation of mechanisms for formation of such a heterogeneous distribution pattern help us to understand the way that substances are distributed in the liver.…”

Section: Introductionmentioning

confidence: 99%

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

Fujii

Miyazaki

Nambu

et al. 1984

European Journal of Drug Metabolism and Pharmacokinetics

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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.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Fujii

Miyazaki

Nambu

et al. 1984

European Journal of Drug Metabolism and Pharmacokinetics

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

Fujii

Miyazaki

Nambu

et al. 1984

European Journal of Drug Metabolism and Pharmacokinetics

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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.

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On the Clinical Pharmacology of Penfluridol

Malmgren

Heykants

1976

Nordisk Psykiatrisk Tidsskrift

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Whole body autoradiographic studies on the distribution of 3H-labeled penfluridol (3H-TLP-607) in mice and rats.

Cited by 3 publications

References 0 publications

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

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

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

On the Clinical Pharmacology of Penfluridol

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