Characteristics and clinical implications of the pharmacokinetic profile of ibuprofen in patients with knee osteoarthritis

Introduction: Ibuprofen is a nonselective cyclooxygenase (COX)-1/COX-2 inhibitorused to treat pain conditions and inflammation. Limited data have been publishedconcerning the pharmacokinetic profile and clinical effects of ibuprofen in patients withosteoarthritis (OA).Aim: In this paper we compared pharmacokinetic and clinical profile of ibuprofen (from800 up to 1800 mg/day tablets) administered in patients affected by severe knee OA.Methods: Ibuprofen was administered for 7 days to patients who were scheduled toundergo knee arthroplasty due to OA. After 7 days, the ibuprofen concentration inplasma and synovial fluid was measured through both High-performance liquidchromatography (HPLC)-UV and gas chromatography-mass spectroscopy (GC/MS),while clinical effects were evaluated through both Visual Analogue Scale (VAS) andWestern Ontario and McMaster Universities (WOMAC) scores.The Naranjo scale and the WHO causality assessment scale were used for estimatingthe probability of adverse drug reactions (ADRs). The severity of ADRs was assessedby modified Hartwig and Siegel scale.Results: Ibuprofen showed a dose-dependent diffusion in both plasma and synovialfluid, which was related to the reduction of pain intensity and improvement of healthstatus, without the development of ADRs.Conclusions: Ibuprofen at higher dosages can be expected to provide better control of OA symptoms as a result of higher tissue distribution.