Sulindac sulphide

Sulforal, 992 Sulforidazine, 980 (metabolite), 738, 1020 Sulformethoxine, 978 Sulforthomidine, 978 Sulfotrimin, 988 Sulfuno, 991 Sulginum, 986 Sulindac, 981 Sulindac sulphide, 981 Sulindac sulphone, 981 Sulla, 989 Sulmycin, 637 Sulpha..., see also under Sulphacalyre, 981 Sulphacarbamide, 995 Sulphacetamide, 981 Sulphacetamide sodium, 981 Sulphacetamide, soluble, 981 Sulphachlorpyridazine, 982 Sulphadiazine, 982 Sulphadiazine sodium, 983 Sulphadiazine, soluble, 983 Sulphadimethoxine, 983 Sulphadimethyloxazole, 991 Sulphadimethylpyrimidine, 984... 

While all NSAIDs have the potential for inducing renal failure, there has been speculation of quantitative differences among the individual NSAIDs. Sulindac was thought to be renal sparing, possibly because of its unusual metabolic pathway [29, 77-79]. The parent compound, sulindac sulphoxide, is an inactive prodrug, which undergoes hepatic metabolism to sulindac sulphide, the metabolite responsible for its anti-inflammatory activity. Sulindac sulphoxide is also metabolized to a much lesser extent to an inactive metabolite, sulindac sulphone. It was hypothesized that, within the human kidney, sulindac sulphide was reversibly oxidized to the inactive parent compound, sulindac sulphoxide, with the result that renal prostaglandin production was not perturbed [29, 78]. 

The combined RIA-technique and isotope dilution has been successfully developed to estimate SULINDAC along with its two prominent metabolites, namely its sulphone and its sulphide present in the plasma-level as shown in the following chemical structures X and Y. 

Quantification. High Pressure Liquid Chromatography. In plasma or urine sulindac and its sulphide and sulphone metabolites, sensitivity 100 ng/ml in plasma, UV detection—B. 

Following daily oral doses of 200 mg, twice a day to 12 subjects, mean maximum steady-state plasma concentrations were sulindac S.Opg/ml, sulphide 6.9 ig/ml, sulphone 2.6pg/ml a diurnal variation in plasma concentrations was reported with lower concentrations being attained after the evening dose. After oral administration of 400 mg once daily to 12 subjects, maximum steady-state plasma concentrations were sulindac 8.7 ig/ml, sulphide 8.8 pg/ml, sulphone 3.9 ig/ml (B. N. Swanson et al., Clin. Pharmac. Ther., 1982, 32, 397-403). 

Half-life. Plasma half-life, sulindac about 7 hours, sulphide metabolite about 16 to 18 hours. 

Protein Binding. In plasma, sulindac, sulphone, and sulphide, about 95%. 

Nevertheless, sulindac is the preferred compound for clinical applications an oral dosage of this inactive bioprecursor will circumvent initial exposure of gastric and intestinal mucosa to the active drug, and might thus provide a therapeutic advantage in comparison with the sulphide dosing. 

The drug gets absorbed invariably to the extent of 90% after the oral administration. The peak plasma levels are usually accomplished in about 2 hour in the fasting patient and may be extended between 3-4 hours when given with food. It has been duly observed that the mean half-life of sulindac is 7 = 8 hours and the mean half-life of the corresponding sulphide-metabolite is 16.4 hour (almost double than the parent drug). 

In 6 healthy subjects colestyramine 4 g twice daily with meals was found to reduce the AUC of a simultaneous single 400-mg dose of sulindac by 78% the AUC of its sulfide metabolite was reduced by 84%. Even when the sulindac was given 3 hours before the colestyramine, its AUC of colestyramine and its sulphide metabolite were reduced by 44% and 55%, respectively. ... 

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