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Xenobiotica. 2013 May;43(5):443-53. doi: 10.3109/00498254.2012.734642. Epub 2012 Nov 16.

Bioavailability, metabolism and disposition of oral pazopanib in patients with advanced cancer.

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1
Department of Drug Metabolism and Pharmacokinetics, GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA. yanli.2.deng@gsk.com

Abstract

1. Pazopanib (Votrient) is an oral tyrosine kinase inhibitor that was recently approved for the treatment of renal cell carcinoma and soft tissue sarcoma. 2. In this two-part study, we investigated the metabolism, disposition of [(14)C]pazopanib, and the oral bioavailability of pazopanib tablets in patients with advanced cancer. 3. In part A, three men each received a single oral dose of [(14)C]pazopanib in suspension (400 mg, 70 ┬ÁCi). Pazopanib was the predominant drug-related component in circulation. Two metabolites derived from hydroxylation and one from N-demethylation were also circulating, but were minor, each accounting for <5% of plasma radioactivity. Faecal elimination predominated, accounting for 82.2% of the administered radio-dose, with negligible renal elimination (2.6% of dose). Pazopanib was primarily excreted as the unchanged drug in faeces (67% of dose). 4. In part B, seven additional patients received a single intravenous administration of 5 mg pazopanib (day 1) followed by oral administration of 800 mg pazopanib tablet once daily for 26 days (days 3 or 5-28). In the three evaluable patients from part B, pazopanib had a slow plasma clearance and a small volume of distribution. The absolute oral bioavailability of the 800 mg pazopanib tablet ranged from 14% to 39%.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00478725.

PMID:
23548165
DOI:
10.3109/00498254.2012.734642
[Indexed for MEDLINE]
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