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Xenobiotica. 2013 Sep;43(9):823-35. doi: 10.3109/00498254.2013.767951. Epub 2013 Feb 7.

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

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1
CNS&Pain iMed Science Södertälje, AstraZeneca Research and Development, Södertälje, Sweden. Johanna.Haglund@bredband.net

Abstract

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 ¹⁴C 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 ¹⁴C material into the stomach. 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. 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. 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.

PMID:
23391212
DOI:
10.3109/00498254.2013.767951
[Indexed for MEDLINE]
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