The pharmacokinetic profile of sitaxsentan, a selective endothelin receptor antagonist, in varying degrees of renal impairment.
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.
Dhaun
Neeraj
N
Clinical Pharmacology Unit, University of Edinburgh, Queen's Medical Research Unit, Edinburgh, UK. bean.dhaun@ed.ac.uk
Melville
Vanessa
V
Kramer
William
W
Stavros
Fiona
F
Coyne
Terrance
T
Swan
Suzanne
S
Goddard
Jane
J
Webb
David J
DJ
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
D065130:Endothelin A Receptor Antagonists; D007555:Isoxazoles; D044022:Receptor, Endothelin A; D013876:Thiophenes; C106276:sitaxsentan