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

J Am Soc Nephrol. 1992 Feb;2(8):1285-90. doi: 10.1681/ASN.V281285.

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 less than 0.01), as measured by gas chromatography/mass spectrometry. CGS 12970 had no significant effect on urinary 6-keto-prostaglandin F1 alpha 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.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Administration, Oral
  • Adult
  • Cyclosporine / adverse effects*
  • Cyclosporine / pharmacokinetics
  • Eicosanoids / urine
  • Female
  • Hemodynamics / physiology
  • Humans
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Kidney Diseases / chemically induced
  • Kidney Diseases / metabolism
  • Kidney Diseases / physiopathology
  • Kidney Diseases / prevention & control
  • Kidney Transplantation*
  • Male
  • Pilot Projects
  • Pyridines / pharmacokinetics
  • Pyridines / therapeutic use*
  • Thromboxane-A Synthase / antagonists & inhibitors*

Substances

  • Eicosanoids
  • Pyridines
  • Cyclosporine
  • 3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid
  • Thromboxane-A Synthase