Clinical pharmacokinetics of sulindac. A dynamic old drug

Clin Pharmacokinet. 1997 Jun;32(6):437-59. doi: 10.2165/00003088-199732060-00002.

Abstract

Sulindac is a nonsteroidal anti-inflammatory drug (NSAID) of the indene acetic acid class. The absorption of sulindac is rapid when given orally. Sulindac is reversibly metabolised to sulindac sulphide which has anti-inflammatory and analgesic properties and is irreversibly metabolised to sulindac sulphone which has been suggested to possess antiproliferative effects against tumours. Sulindac and its sulphide and sulphone metabolites bind extensively to plasma albumin. Sulindac is eliminated following bio-transformation; sulindac and sulindac sulphone and their respective glucurooconjugated metabolites are excreted in urine; however only a small amount of the sulindac sulphide metabolite is eliminated in urine. Following long term twice daily administration both sulindac and its metabolites accumulate in plasma. Both patients with cirrhosis and the elderly demonstrate elevated concentrations of all species upon long term sulindac administration as compared with a single dose. The disposition of sulindac and its metabolites may be tied to renal function. In end-stage renal disease, increased free fractions of all species and accumulation of the sulphide and sulphone metabolites, and to a lesser extent sulindac, occurs. Significant drug interactions have been demonstrated for dimethylsulphoxide, cyclosporin, furosemide (frusemide), hydrochlorothiazide, methotrexate and cholestyramine.

Publication types

  • Review

MeSH terms

  • Absorption
  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Drug Interactions
  • Humans
  • Kidney / drug effects
  • Kidney / metabolism
  • Liver / metabolism
  • Middle Aged
  • Protein Binding
  • Serum Albumin / metabolism
  • Sulindac / pharmacokinetics*
  • Sulindac / pharmacology
  • Sulindac / therapeutic use
  • Synovial Fluid / metabolism
  • Tissue Distribution

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Serum Albumin
  • Sulindac