CLINICAL PHARMACOKINETICS OF SULINDAC - A DYNAMIC OLD DRUG

Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) of the inden e acetic acid class. The absorption of sulindac is rapid when given or ally. Sulindac is reversibly metabolised to sulindac sulphide which ha s anti-inflammatory and analgesic properties and is irreversibly metab olised to sulindac sulphone which has been suggested to possess antipr oliferative effects against tumours. Sulindac and its sulphide and sul phone metabolites bind extensively to plasma albumin. Sulindac is elim inated following bio-transformation; sulindac and sulindac sulphone an d their respective glucurooconjugated metabolites are excreted in urin e; however only a small amount of the sulindac sulphide metabolite is eliminated in urine. Following long term twice daily administration bo th sulindac and its metabolites accumulate in plasma. Both patients wi th cirrhosis and the elderly demonstrate elevated concentrations of al l species upon long term sulindac administration as compared with a si ngle dose. The disposition of sulindac and its metabolites may be tied to renal function. In end-stage renal disease, increased free fractio ns of all species and accumulation of the sulphide and sulphone metabo lites, and to a lesser extent sulindac, occurs. Significant drug inter actions have been demonstrated for dimethylsulphoxide, cyclosporin, fu rosemide (frusemide), hydrochlorothiazide, methotrexate and cholestyra mine.