The pharmacokinetic profile of sitaxsentan, a selective endothelin receptor antagonist, in varying degrees of renal impairment

Neeraj Dhaun, Vanessa Melville, William Kramer, Fiona Stavros, Terrance Coyne, Suzanne Swan, Jane Goddard, David J Webb

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)733-7
Number of pages5
JournalBritish Journal of Clinical Pharmacology
Volume64
Issue number6
DOIs
Publication statusPublished - Dec 2007

Keywords

  • Adolescent
  • Adult
  • Aged
  • Endothelin A Receptor Antagonists
  • Female
  • Humans
  • Isoxazoles
  • Kidney Diseases
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Receptor, Endothelin A
  • Thiophenes

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