Pharmacokinetics of Non‐Steroidal Anti‐Inflammatory Agents

Summary: Pharmacokinetics of non‐steroidal anti‐inflammatory agents. G. D. Champion and G. G. Graham, Aust. N.Z. J. Med., 1978, 8, Suppl. 1, pp 94–100. The non‐steroidal anti‐inflammatory drugs (NSAID) are well absorbed from the gastrointestinal tract. The only known exception is aspirin. The availability of aspirin is 70% or less due to hydrolysis in the gastrointestinal tract or during first pass through the liver. However, the remainder is absorbed as its pharmacologically active metabolite, salicylate. The NSAID are extensively bound to plasma proteins but the clinical significance of interactions between NSAID due to displacement from plasma proteins is not known. The two compartment open model generally describes the disposition of the NSAID. Both the volume of distribution (Vd ss ) and clearance of NSAID are low, the volume of distribution being below 0.2 1/kg and clearance below 200 ml/minute in most cases. The concentrations of NSAID in synovial fluid increase slowly after single doses then decrease with similar half‐lives to the terminal ha If‐lives in plasma. Nonlinear kinetics with greater than predicted accumulation occurs with salicylate, sulindac sulphide and possibly alclofena. By contrast, at high doses, the accumulation of naproxen and phenylbutazone is less than predicted. Approximately 50% of doses of azapropazone are excreted unchanged but other NSAID are inactivated by hepatic metabolism and little of the NSAID are excreted unchanged in urine. Because of interpatient differences in pharmacokinetics, dosage regimens of NSAID should be individualised.