Effects of sulindac on renal and extrarenal eicosanoid synthesis.
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.
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
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