Tissue Distribution and Excretion of Amodiaquine in the Rat
Identifieur interne : 003230 ( Main/Exploration ); précédent : 003229; suivant : 003231Tissue Distribution and Excretion of Amodiaquine in the Rat
Auteurs : P. A. Winstanley [Royaume-Uni] ; G. Edwards [Royaume-Uni] ; C. G. Curtis ; M. L'E. Orme ; G. M. Powell ; A. M. BreckenridgeSource :
- Journal of Pharmacy and Pharmacology [ 0022-3573 ] ; 1988-05.
Abstract
Abstract— 14C‐Labelled amodiaquine ([14C]AQ) has been administered to male Wistar rats by oral and intravenous routes (n = 6 for each route of administration). Excretion of total 14C‐activity was predominantly in the faeces after both oral and intravenous administration. After oral administration 86 ± 8.3% (mean ± s.d.) of the 14C administered had been excreted (77 ±9% in the faeces, 7 ± 1 % in the urine and 2 ± 2% in cage washings) over 72 h. Of the 14C administered, 4 ± 1% was recovered from the tissues, and this was widely distributed, with the main organs of accumulation being kidney, liver, red bone marrow and spleen. After intravenous administration, 102.6 ± 9.7% of the 14C had been excreted (90.9 ± 9.6% in faeces, 10.9 ± 0.8% in urine and 0.5 ± 0.2% in cage washings) over 72 h. High‐performance liquid chromatographic analysis of urine and faeces samples following oral administration of 14C‐AQ (8.6 mg kg−1; base) revealed recoveries of 210 ± 70 μg amodiaquine (AQ) and 123 ± 32 μg desethylamodiaquine (AQm) in the faeces, and 2.4 ± 0.5 μg AQ and 18.5 ± 4.1 μg AQm in the urine. Female Wistar rats (n = 6) each received [14C]AQ orally and were killed at the following times: 0.5, 1, 3, 6, 24 and 48 h. Autoradiographs were prepared from each animal and these revealed significant amounts of radioactivity in the tissues at 48 h. This was accumulated maximally by liver and kidney. Radioactivity was detected in bone marrow at 48 h. These data show that after oral administration of [14C]AQ to rats, significant amounts of radiolabel were accumulated in the liver, and haemopoietic tissues, which are the sites of observed toxicity in man. Of the excreted radiolabel, only a small proportion was in the form of AQ or AQm.
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DOI: 10.1111/j.2042-7158.1988.tb05264.x
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A." last="Winstanley">P. A. Winstanley</name><affiliation></affiliation><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Correspondence address: Dept of Pharmacology and Therapeutics, University of Liverpool, New Medical Building, Ashton Street, P.O. Box 147, Liverpool L69 3BX</wicri:regionArea><wicri:noRegion>Liverpool L69 3BX</wicri:noRegion></affiliation></author><author><name sortKey="Edwards, G" sort="Edwards, G" uniqKey="Edwards G" first="G." last="Edwards">G. Edwards</name><affiliation wicri:level="1"><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Parasitology, Liverpool School of Tropical Medicine, Liverpool L3 5QA</wicri:regionArea><wicri:noRegion>Liverpool L3 5QA</wicri:noRegion></affiliation><affiliation></affiliation></author><author><name sortKey="Curtis, C G" sort="Curtis, C G" uniqKey="Curtis C" first="C. G." last="Curtis">C. G. 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Breckenridge</name><affiliation><wicri:noCountry code="subField">3BX</wicri:noCountry></affiliation></author></analytic><monogr></monogr><series><title level="j" type="main">Journal of Pharmacy and Pharmacology</title><title level="j" type="alt">JOURNAL OF PHARMACY AND PHARMACOLOGY</title><idno type="ISSN">0022-3573</idno><idno type="eISSN">2042-7158</idno><imprint><biblScope unit="vol">40</biblScope><biblScope unit="issue">5</biblScope><biblScope unit="page" from="343">343</biblScope><biblScope unit="page" to="349">349</biblScope><biblScope unit="page-count">7</biblScope><publisher>Blackwell Publishing Ltd</publisher><pubPlace>Oxford, UK</pubPlace><date type="published" when="1988-05">1988-05</date></imprint><idno type="ISSN">0022-3573</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0022-3573</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract— 14C‐Labelled amodiaquine ([14C]AQ) has been administered to male Wistar rats by oral and intravenous routes (n = 6 for each route of administration). Excretion of total 14C‐activity was predominantly in the faeces after both oral and intravenous administration. After oral administration 86 ± 8.3% (mean ± s.d.) of the 14C administered had been excreted (77 ±9% in the faeces, 7 ± 1 % in the urine and 2 ± 2% in cage washings) over 72 h. Of the 14C administered, 4 ± 1% was recovered from the tissues, and this was widely distributed, with the main organs of accumulation being kidney, liver, red bone marrow and spleen. After intravenous administration, 102.6 ± 9.7% of the 14C had been excreted (90.9 ± 9.6% in faeces, 10.9 ± 0.8% in urine and 0.5 ± 0.2% in cage washings) over 72 h. High‐performance liquid chromatographic analysis of urine and faeces samples following oral administration of 14C‐AQ (8.6 mg kg−1; base) revealed recoveries of 210 ± 70 μg amodiaquine (AQ) and 123 ± 32 μg desethylamodiaquine (AQm) in the faeces, and 2.4 ± 0.5 μg AQ and 18.5 ± 4.1 μg AQm in the urine. Female Wistar rats (n = 6) each received [14C]AQ orally and were killed at the following times: 0.5, 1, 3, 6, 24 and 48 h. Autoradiographs were prepared from each animal and these revealed significant amounts of radioactivity in the tissues at 48 h. This was accumulated maximally by liver and kidney. Radioactivity was detected in bone marrow at 48 h. These data show that after oral administration of [14C]AQ to rats, significant amounts of radiolabel were accumulated in the liver, and haemopoietic tissues, which are the sites of observed toxicity in man. Of the excreted radiolabel, only a small proportion was in the form of AQ or AQm.</div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country></list><tree><noCountry><name sortKey="Breckenridge, A M" sort="Breckenridge, A M" uniqKey="Breckenridge A" first="A. M." last="Breckenridge">A. M. Breckenridge</name><name sortKey="Curtis, C G" sort="Curtis, C G" uniqKey="Curtis C" first="C. G." last="Curtis">C. G. Curtis</name><name sortKey="Orme, M L E" sort="Orme, M L E" uniqKey="Orme M" first="M. L'E." last="Orme">M. L'E. Orme</name><name sortKey="Powell, G M" sort="Powell, G M" uniqKey="Powell G" first="G. M." last="Powell">G. M. Powell</name></noCountry><country name="Royaume-Uni"><noRegion><name sortKey="Winstanley, P A" sort="Winstanley, P A" uniqKey="Winstanley P" first="P. A." last="Winstanley">P. A. Winstanley</name></noRegion><name sortKey="Edwards, G" sort="Edwards, G" uniqKey="Edwards G" first="G." last="Edwards">G. Edwards</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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