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) > or = 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 < or = 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 C(max) (10.3-13.9 microg ml(-1)), AUC(infinity) (18.7-22.5 h microg(-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 (t(1/2), 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.
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) > or = 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 < or = 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 C(max) (10.3-13.9 microg ml(-1)), AUC(infinity) (18.7-22.5 h microg(-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 (t(1/2), 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.
Authors: C Wu; M F Chan; F Stavros; B Raju; I Okun; S Mong; K M Keller; T Brock; T P Kogan; R A Dixon Journal: J Med Chem Date: 1997-05-23 Impact factor: 7.446