Disposition of [14C]LY2606368 following intravenous administration in patients with advanced and/or metastatic solid tumours.

Disposition of [14C]LY2606368 following intravenous administration in patients with advanced and/or metastatic solid tumours.
Xenobiotica. 2019 Dec 17;:1-12
Authors: Wickremsinhe ER, Hynes SM, Payne CD, Guo Y, Cassidy KC
Abstract
The disposition and metabolism of prexasertib, a CHK-1 inhibitor was characterised over a 120 h period following a single 170-mg intravenous dose of [14C]prexasertib (50 µCi) to 6 patients with advanced/metastatic solid tumours.The prexasertib safety profile was consistent with prior studies. Plasma, urine, and faeces were analysed for radioactivity, prexasertib, and metabolites. Geometric mean t1/2 in plasma was 34.2 h for prexasertib and 73.8 h for total radioactivity. Unchanged prexasertib accounted for approximately 9% of plasma total radioactivity, indicating extensive metabolism by the presence of circulating metabolites. Both renal and faecal excretion were identified as important routes of elimination since 41.8% (±12.9%) of the total administered radioactivity was recovered in the renal excretions and 32.2% (±7.28%) in the faecal excretions. Mean renal clearance was approximately 15% of the total systemic clearance, while biliary clearance was also low. Prexasertib was cleared predominantly by metabolism with only 23% of the dose recovered in excreta as intact drug. Radioactivity was eliminated predominantly within 72 h in urine, but faecal elimination was protracted.The metabolism of pre...

Source: Xenobiotica - December 16, 2019 Category: Research Authors: Wickremsinhe ER, Hynes SM, Payne CD, Guo Y, Cassidy KC Tags: Xenobiotica Source Type: research