ADME characterization in rats revealed immediate secretion of AZD7903 into the stomach after IV dosing

1. The distribution of AZD7903 and/or its metabolites was studied in rats following a single p.o. or i.v. dose using quantitative whole-body autoradiography (QWBA). At 5 min after i.v. administration of the C-14 compound, high levels of radioactivity were observed in the fundus of the stomach compared to blood and plasma and the rest of the stomach, indicating an active secretion of C-14 material into the stomach. 2. Also, excretion and pharmacokinetics were studied following p.o. and i.v. dosage in rats. The radioactivity was mainly excreted via feces, and even in i. v. administered bile-duct cannulated (BDC) animals a significant part of radioactivity (26% in males and 57% in females) was recovered in the feces in the form of parent compound and two minor metabolic products. 3. The compound was well absorbed (F% 98 in males and 76 in females), and showed low clearance in plasma (0.14 L/h/kg in males and 0.03 L/h/kg in females) and low-intermediate Vd(ss) (0.7 L/kg). Clear differences in metabolic pathways (qualitative) and rates (quantitative) and consequently in PK parameters between sexes were observed. 4. In summary, the results indicate AZD7903 being substrate for a transporter protein and support the hypothesis that the differences in disposition between sexes are due to differences in metabolic pathways and rates.