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            <title xml:lang="en">Pharmacokinetics and tissue distribution of the antileukaemic organoarsenicals arsthinol and melarsoprol in mice</title>
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                <term xml:lang="en"> Leukaemia</term>
                <term xml:lang="en"> Pharmacokinetics</term>
                <term xml:lang="en"> Arsenic</term>
                <term xml:lang="en"> Melarsoprol</term>
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              <p>Melarsoprol and arsthinol have been shown to be effective on various leukaemia cell lines. Nevertheless, the tissue distribution of these compounds remains a key point since the bone marrow is considered as the site of action and the central nervous system as the site of the main toxicity. In this study, we have determined the exposure of each organ (blood, liver, bone marrow and brain) to arsenic, irrespectively of the exact nature of arsenic species contained by the organ.In the bone marrow, arsenic concentrations were very high, especially that of melarsoprol. However, the lower ability of arsthinol to concentrate in the bone marrow could be compensated by its higher antileukaemic activity.The brain concentrations were high, although lower than in the bone marrow; this fact is in very good accordance with the observation that the brain is mainly involved in the acute toxicity of trivalent organoarsenicals.</p>
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