Clinical pharmacokinetics of diclofenac. Therapeutic insights and pitfalls

Clin Pharmacokinet. 1997 Sep;33(3):184-213. doi: 10.2165/00003088-199733030-00003.

Abstract

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phenylacetic acid class. When given orally the absorption of diclofenac is rapid and complete. Diclofenac binds extensively to plasma albumin. The area under the plasma concentration-time curve (AUC) of diclofenac is proportional to the dose for oral doses between 25 to 150 mg. Substantial concentrations of drug are attained in synovial fluid, which is the proposed site of action for NSAIDs. Concentration-effect relationships have been established for total bound, unbound and synovial fluid diclofenac concentrations. Diclofenac is eliminated following biotransformation to glucoroconjugated and sulphate metabolites which are excreted in urine, very little drug is eliminated unchanged. The excretion of conjugates may be related to renal function. Conjugate accumulation occurs in end-stage renal disease; however, no accumulation is apparent upon comparison of young and elderly individuals. Dosage adjustments for the elderly, children or for patients with various disease states (such as hepatic disease or rheumatoid arthritis) may not be required. Significant drug interactions have been demonstrated for aspirin (acetylsalicylic acid), lithium, digoxin, methotrexate, cyclosporin, cholestyramine and colestipol.

Publication types

  • Review

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Area Under Curve
  • Chronobiology Phenomena
  • Diclofenac / administration & dosage
  • Diclofenac / metabolism
  • Diclofenac / pharmacokinetics*
  • Diclofenac / therapeutic use
  • Dosage Forms
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • Gastrointestinal Transit
  • Humans
  • Intestinal Absorption / drug effects
  • Male
  • Middle Aged
  • Synovial Fluid / metabolism
  • Tissue Distribution

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Dosage Forms
  • Diclofenac