Figure 4 from Mechanisms Underlying Cedazuridine-Mediated Enhancement of Oral Decitabine Bioavailability

Le résumé fourni par la source

CNT1 deletion reduces systemic decitabine exposure and increases renal loss. A, Schematic of the uptake assay design using HEK293 cells stably overexpressing CNT1. [3H]-decitabine uptake was measured to assess CNT1-mediated transport. B, [3H]-decitabine uptake in CNT1-overexpressing cells (CNT1 OE) compared with vector control (VC). CNT1 significantly enhanced decitabine uptake up to 10-fold, confirming its role as a renal transporter of decitabine. C, Plasma concentration–time profiles of decitabine administered orally with oral co-cedazuridine in WT vs. CNT1-KO mice. CNT1-KO mice exhibited reduced systemic exposure compared with WT. D, Urinary cumulative radioactivity expressed as percentage of total administered dose following oral administration of decitabine (10 mg/kg) and cedazuridine (3 mg/kg) in WT and CNT1-KO mice (P < 000.1). CNT1-KO mice exhibited ∼1.8-fold higher urinary recovery compared with WT animals (P < 0.0001), consistent with impaired tubular reabsorption of decitabine. Data are presented as mean ± SEM (n = 5 per group for in vivo studies; n = 3 per group for uptake assay and mass balance study). **, P < 0.01; ****, P < 0.0001.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.