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• W3186169227 abstract "Raloxifene undergoes extensive glucuronidation in the gastrointestinal (GI) tract and the liver. However, the impact of age on raloxifene disposition has never been studied. The purpose of this paper is to determine glucuronidation and Pharmacokinetics (PK) profiles of raloxifene in rats at different ages.Raloxifene glucuronidation was characterized using S9 fractions prepared from different intestinal segments and the liver of F344 rats at 4-, 11-, and 28-week. PK studies were conducted to determine raloxifene oral bioavailability at different ages. Raloxifene and its glucuronides were quantified using LC-MS/MS.Raloxifene-6-glucuronide and raloxifene-4'-glucuronide were detected as the major metabolites and the ratio of these two glucuronides were different ranging from 2.1 to 4.9 folds in the ileum, jejunum, liver, and duodenum, and from 14.5 to 50 folds in the colon. The clearances in the duodenum at 4-week for both two glucuronides were significantly lower than those at the other two ages. PK studies showed that the oral bioavailability of raloxifene is age dependent. The absolute oral bioavailability of raloxifene was 3.5-folds higher at 4-week compared to that at 11-weeks. When raloxifene was administered through IV bolus, its half-life was 5.9 ± 1.16 h and 3.7 ± 0.68 h at 11-and 4-week, respectively.These findings suggested that raloxifene metabolism in the duodenum was significantly slower at young age in rats, which increased the oral bioavailability of raloxifene. At 11-week, enterohepatic recycling efficiency was higher than that of 4-week. Raloxifene's dose at different ages should be carefully considered." @default.
• W3186169227 created "2021-08-02" @default.
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• W3186169227 date "2021-07-28" @default.
• W3186169227 modified "2023-10-09" @default.
• W3186169227 title "Age-and Region-Dependent Disposition of Raloxifene in Rats" @default.
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• W3186169227 doi "https://doi.org/10.1007/s11095-021-03084-y" @default.
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