Reduction of oral bioavailability of paracetamol by tolmetin in rat.

The pharmacokinetics of paracetamol alone and coadministered with tolmetin were studied in male Wistar rats. Open pharmacokinetic model of one and two compartments were fitted to experimental average plasma levels of paracetamol. Simultaneously fittings (intravenous and oral curves showed significant statistical differences for bioavailability estimated parameters (AUCev, F and K01). Also significant statistical differences were found for alfa, beta, K21 and Vd(ss) estimated parameters. Oral paracetamol bioavailability reduction (24%) was observed by coadministration of tolmetin in the rat. Since AUCiv and plasma clearance of paracetamol remained unchanged after intravenous coadministration, may be suggested that absorption process seems responsible of paracetamol bioavailability reduction.