Relationships between thromboxane production, platelet aggregability, and serum concentrations of ibuprofen or...

Arachidonate-induced ex vivo platelet aggregations were performed before and after subjects received various doses of either ibuprofen or flurbiprofen. Both ibuprofen and flurbiprofen reduced the initial rate of thromboxane B2 (TxB2) production, but about 10% of control TxB2 production was refractory to either drug. Aggregation was observed after TxB2 concentrations exceeded a threshold of about 40 ng/ml. Once the threshold was achieved, aggregation and TxB2 production occurred independently of either drug. Ibuprofen and flurbiprofen concentrations of about 3 and 0.2 micrograms/ml, respectively, inhibited aggregation during the 5-minute testing period. A pharmacodynamic model was developed that predicts TxB2 production, aggregation lag times, and percent aggregation as a function of the time course of drug concentrations in serum.