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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)

journal of the american society of nephrology

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.