title: Effects of sulindac on renal and extrarenal eicosanoid synthesis.
abstract: We measured the renal and extrarenal synthesis of prostacyclin and thromboxane A2, as reflected by the urinary excretion of the stable hydration products 6-keto-prostaglandin F 1 alpha and thromboxane B2 and the corresponding 2,3-dinor-derivatives, during chronic administration of sulindac (200, 400, 600, and 800 mg/day, each dose given for 7 days in successive weeks) in seven healthy subjects. Urinary eicosanoids were measured by negative ion, chemical ionization-GC/MS-validated RIA techniques. Both 2,3-dinor-thromboxane B2 and 2,3-dinor-6-keto-prostaglandin F 1 alpha showed a dose-dependent reduction, ranging between 45% and 85%. In contrast, the urinary excretion of 6-keto-prostaglandin F1 alpha and thromboxane B2 did not change significantly throughout the study. These results extend previous observations of a selective sparing of renal cyclooxygenase activity by sulindac in humans and demonstrate that this selectivity is not related to an overall weaker enzyme inhibition.
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives / Q000652:urine; D000284:Administration, Oral; D000328:Adult; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007192:Indenes / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D011863:Radioimmunoassay; D013467:Sulindac / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000031:analogs & derivatives / Q000652:urine
chemical_list: D007192:Indenes; D013467:Sulindac; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C028965:2,3-dinor-thromboxane B2; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; D011464:Epoprostenol