SU-13197 undergoes extensive first-pass metabolism, resulting in highly variable plasma levels after oral administration, which informs its therapeutic dosing regimen.
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High variability in exposure cautions against unmonitored oral dosing; leaves open need for bioavailability or route optimization trials.
The fate of 14 C‐labeled SU‐13197 was investigated in rat and man. In both, the drug was almost completely metabolized and the radioactivity excreted in the urine and feces. The half‐life of the parent drug was shorter than that of the total of the radioactive metabolites, two of which were recognized as maior components. A glucuronide coniugate was present in rat and human urine and excreted in rat bile. In the six subiects investigated, this excreted con;ugated metabolite had a half‐life similar to that of SU‐13197 (16 hours), while the other metabolite had a longer half‐life (44 hours). In 3 sub;ects who received the drug by oral and intravenous administration, more unchanged SU‐13197 was excreted in the urine following intravenous than oral administration, despite comparable absorption of the radioactive label. This suggests that significant amounts of the drug are metabolized during the process of transfer from the gut to the systemic circulation. The data suggest that following oral administration plasma levels may vary as much as tenfold between individuals. A suitable therapeutic regimen is predicted from the data.
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Shand et al. (1971) studied this question.
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