title: The pharmacokinetic profile of sitaxsentan, a selective endothelin receptor antagonist, in varying degrees of renal impairment.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Clinical Pharmacology Unit, University of Edinburgh, Queen's Medical Research Unit, Edinburgh, UK. bean.dhaun@ed.ac.uk
authors.forename: Neeraj
authors.initials: N
authors.lastname: Dhaun
authors.forename: Vanessa
authors.initials: V
authors.lastname: Melville
authors.forename: William
authors.initials: W
authors.lastname: Kramer
authors.forename: Fiona
authors.initials: F
authors.lastname: Stavros
authors.forename: Terrance
authors.initials: T
authors.lastname: Coyne
authors.forename: Suzanne
authors.initials: S
authors.lastname: Swan
authors.forename: Jane
authors.initials: J
authors.lastname: Goddard
authors.forename: David J
authors.initials: DJ
authors.lastname: Webb
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D065130:Endothelin A Receptor Antagonists; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D007674:Kidney Diseases / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D044022:Receptor, Endothelin A / Q000378:metabolism; D013876:Thiophenes / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D065130:Endothelin A Receptor Antagonists; D007555:Isoxazoles; D044022:Receptor, Endothelin A; D013876:Thiophenes; C106276:sitaxsentan