CLINICAL PHARMACOKINETICS OF DICLOFENAC - THERAPEUTIC INSIGHTS AND PITFALLS

Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) of the phe nylacetic acid class. When given orally the absorption of diclofenac i s rapid and complete. Diclofenac binds extensively to plasma albumin. The area under the plasma concentration-time curve (AUC) of diflofenac is proportional to the dose for oral doses between 25 to 150mg. Subst antial concentrations of drug are attained in synovial fluid, which is the proposed site of action for NSAIDs. Concentration-effect relation ships have been established for total bound, unbound and synovial flui d diclofenac concentrations. Diclofenac is eliminated following biotra nsformation to glucoroconjugated and sulphate metabolites which are ex creted in urine, very little drug is eliminated unchanged. The excreti on of conjugates may be related to renal function. Conjugate accumulat ion occurs in end-stage renal disease; however, no accumulation is app arent upon comparison of young and elderly individuals. Dosage adjustm ents for the elderly, children or for patients with various disease st ates (such as hepatic disease or rheumatoid arthritis) may not be requ ired. Significant drug interactions have been demonstrated for aspirin (acetylsalicylic acid), lithium, digoxin, methotrexate, cyclosporin, cholestyramine and colestipol.