Figure 4 from Mechanisms Underlying Cedazuridine-Mediated Enhancement of Oral Decitabine Bioavailability
Year: 2026
Type: other
Abstract: 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.
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W7140186740