Plasma protein binding and interaction studies with benoxaprofen

Abstract

A high proportion of the acidic anti-inflammatory compound benoxaprofen is bound to the plasma proteins of humans and rats (99.8 and 99.3 per cent respectively). The binding did not vary significantly up to total levels of about 120 μg/ml in human plasma or about 40 μg/ml in rat plasma. Above these levels the proportion bound decreased. At 50 μg/ml, more than 90 per cent of benoxaprofen was associated with the albumin fraction of normal human serum. At higher levels, this binding site became saturated and non-specific binding to all proteins appeared to occur. There was no difference between normal and arthritic subjects. In normal rat serum, there was much less bound to albumin. Total binding was reduced in adjuvant arthritic rats. due to decreased binding to α and β 1 globulins. At plasma levels in the range required for therapeutic activity, benoxaprofen did not displace warfarin, salicylate, prednisolone or dexamethasone from their binding to human plasma proteins. In contrast, therapeutic levels of phenylbutazone displaced warfarin.