ArticlePharmaceutical research1998
Effect of coadministered uridine on intestinal first-pass metabolism of 5'-deoxy-5-fluorouridine in conscious rats--an evaluation by method of portal-systemic concentration difference.
Article in Pharmaceutical research, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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3 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
purposeThe effect of uridine (UR) coadministration on the intestinal metabolism from 5'-deoxy-5-fluorouridine (5'-DFUR) to 5-fluorouracil (5-FU) was evaluated by a method of concentration difference between portal and systemic bloods in conscious rats (PS method).
methods5'-DFUR (100 mg/kg) alone (Group A), or 5'-DFUR + UR (100 mg/kg each) (Group B) was orally administered to conscious rats. The portal and arterial bloods were simultaneously withdrawn from two canulas at appropriate time intervals, and blood concentrations of 5'-DFUR, 5-FU, UR and uracil (U) were assayed by HPLC. The concentration-time profiles of these drugs and its metabolites were analyzed by local moment analysis.
resultsUR coadministration made the local absorption ratio (Fa) of 5'-DFUR decrease significantly from 60.1 +/- 10.5% to 38.0 +/- 18.6% of dose. Though the local absorption ratios (Fm(a)) of the metabolite (5-FU) were the same between Group A and Group B (8.3 +/- 1.9 and 8.7 +/- 4.0% of 5'-DFUR, respectively), AUC of arterial 5-FU in Group B was 5 times greater than that in Group A. UR was not detected in the portal blood, and Fm(a) of U was estimated to be 41.9 +/- 26.8% of UR in Group B.
conclusionsIt is predicted that a large portion of 5-FU generated from 5'-DFUR is further degraded in the intestine in Group A, and U generated from UR blocks 5-FU degradation in the intestine and the systemic circulation in Group B.
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