A pilot study to assess the ability of an orally available selective thromboxane synthase inhibitor to improve renal function in cyclosporine-treated renal transplant recipients

Matthew R. Weir, David K. Klassen, James F. Burdick

Research output: Contribution to journalArticle

Abstract

Six cyclosporine (cyclosporine A (CsA))-treated renal transplant patients (4.3 ± 0.6 months posttransplantation) were studied to see if selective urinary thromboxane (TX) inhibition with CGS 12970 (TX synthase inhibitor) would improve renal function and lessen CsA-induced decrements in RPF and GFR as measured by (99Tc)DTPA and (131I)hippuran clearances. The baseline trough CsA levels of the patients were 208 ± 92 ng/mL Before treatment with CGS 12970 (100 mg twice a day for 7 days), all drugs known to affect renal function or CsA pharmacokinetics were stopped. CGS 12970 therapy did not alter RPF (203 ± 17 pre versus 200 ± 15 mL/min post), GFR (38.5 ± 3.2 pre versus 38.2 ± 3.9 mL/min post), or serum creatinine (creat) (1.9 ± .06 pre versus 1.8 ± 0.18 mg/dL post), despite an average of 81% suppression of urine TX (65 ± 14 pg/mg of creat pre versus 12 ± 4 pg/mg of creat post); P < 0.01), as measured by gas chromatography/mass spectrometry. CGS 12970 had no significant effect on urinary 6-keto-prostaglandin F1a levels (63 ± 4 pg/mg of creat pre versus 85 ± 25 pg/mg of creat post). CGS 12970 did not alter CsA pharmacokinetics or drug levels, blood pressure, weight, or serum electrolytes of the patients. These results suggest that: (1) if TX is a mediator in CsA nephrotoxicity, 81% suppression by a selective TX synthase inhibitor may not be sufficient to improve renal function; (2) urinary TxB2 may not necessarily reflect adequate inhibition of TxA2 synthesis in the kidney; or (J) TX is not an important mediator of CsA-mediated reduction in renal function in recently transplanted patients with stable creatinine in the 1.5- to 2.0-mg/dL range.

Original languageEnglish (US)
Pages (from-to)1285-1290
Number of pages6
JournalJournal of the American Society of Nephrology
Volume2
Issue number8
StatePublished - Feb 1 1992

Keywords

  • Cyclosporine
  • Renal function
  • Thromboxane

ASJC Scopus subject areas

  • Nephrology

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