title: 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.
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)
authors.affiliation: Department of Medicine, University of Maryland Hospital, Baltimore 21201.
authors.forename: M R
authors.initials: MR
authors.lastname: Weir
authors.forename: D K
authors.initials: DK
authors.lastname: Klassen
authors.forename: J F
authors.initials: JF
authors.lastname: Burdick
mesh_terms: D000284:Administration, Oral; D000328:Adult; D016572:Cyclosporine / Q000009:adverse effects* / Q000493:pharmacokinetics; D015777:Eicosanoids / Q000652:urine; D005260:Female; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D016030:Kidney Transplantation; D008297:Male; D010865:Pilot Projects; D011725:Pyridines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
chemical_list: D015777:Eicosanoids; D011725:Pyridines; D016572:Cyclosporine; C049113:3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid; D013930:Thromboxane-A Synthase