Abstract

Bosentan, clazosentan, and tezosentan are three small-molecule endothelin receptor antagonists (ERAs), displacing endothelin-1 (ET-1) from its binding site. Atarget-mediated drug disposition (TMDD) pharmacoki-netic (PK) model described the non-linearity in the PKof bosentan caused by its high receptor binding affinitywith time-dependent varying receptor expression or re-appearance. The aim of this analysis was to investigate the presence of TMDD for clazosentan and tezosentan and to corroborate the hypothesis of a diurnal receptor synthesis.

By Anke-Katrin Volz,  Jasper Dingemanse,  Andreas Krause, Thorsten Lehr