Interrogating the relationship between rat in vivo tissue distribution and drug property data for >200 structurally unrelated molecules.

The ability to explain distribution patterns from drug physicochemical properties and binding characteristics has been explored for more than 200 compounds by interrogating data from quantitative whole body autoradiography studies (QWBA). These in vivo outcomes have been compared to in silico and in vitro drug property data to determine the most influential properties governing drug distribution. Consistent with current knowledge, in vivo distribution was most influenced by ionization state and lipophilicity which in turn affected phospholipid and plasma protein binding.

Trametinib, a first-in-class oral MEK inhibitor mass balance study with limited enrollment of two male subjects with advanced cancers.

1. This study assessed the mass balance, metabolism and disposition of [(14)C]trametinib, a first-in-class mitogen-activated extracellular signal-related kinase (MEK) inhibitor, as an open-label, single solution dose (2 mg, 2.9 MBq [79 µCi]) in two male subjects with advanced cancer.

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

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.