The pharmacokinetic profile of sitaxsentan, a selective endothelin receptor antagonist, in varying degrees of renal impairment
Year: 2007
Type: article
Study design: Clinical Trial
Abstract: What is already known about this subject • The initial indication for endothelin (ET) receptor antagonism as a treatment strategy, primary pulmonary hypertension, is now expanding to include scleroderma, which can cause both pulmonary and renal disease. • It is important to understand the effects of impaired renal function on the pharmacokinetics of these drugs to allow appropriate dosing in individuals with impaired renal function. What this study adds • Sitaxsentan, an oral selective endothelin A receptor antagonist, is licensed for the treatment of pulmonary hypertension, and studies of this drug in CKD are planned. • The pharmacokinetic profile of sitaxsentan is unchanged in subjects with varying degrees of renal impairment. • The results of this study will allow confident dosing of sitaxsentan in individuals with renal impairment, and inform future studies. Aim To investigate the pharmacokinetic profile of a single 100‐mg oral dose of sitaxsentan, a selective endothelin type A receptor antagonist, in subjects with normal and impaired renal function. Methods This was an open label, single oral dose study in subjects with normal [creatinine clearance (CrCL) ≥ 80 ml min−1] and impaired renal function (mild renal impairment CrCL 51–80 ml min−1, moderate impairment CrCL 31–50 ml min−1, severe impairment CrCL ≤ 30 ml min−1). All subjects received a dose of 100 mg sitaxsentan. Results Twenty‐four subjects were enrolled, six in each of the normal and three renal impairment groups. The mean plasma sitaxsentan concentrations were comparable across the groups, as were the mean values for Cmax (10.3–13.9 µg ml−1), AUC∞ (18.7–22.5 h µg−1 ml−1), oral clearance (CL/F, 82.3–94.9 ml min−1), volume of distribution (Vz/F, 64.8–69.6 l) and elimination half‐life (t1/2, 8.6–9.6 h). There was substantial overlap among the four groups in the individual subject values for CL/F and Vz/F and no relationship between either of these parameters and CrCL. Conclusion After a single 100‐mg oral dose of sitaxsentan there were no differences in its pharmacokinetics among subjects with normal or impaired renal function.
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2006040668