The aim of this study was to investigate the effect of pentoxifylline (PTX), an antiplatelet agent, on the pharmacokinetics of rosiglitazone (RSG) in rats. Pharmacokinetic parameters of RSG were determined in rats after oral administration (3 mg/kg/day) in the presence and absence of PTX (10 mg/kg) 3 times daily. Compared to control animals, rats pretreated with PTX for 7 days had a decrease in RSG peak plasma concentration (Cmax) of 19% with no change in the values of the area under the concentration-time curve (AUC). Alternatively, rats coadministered single-dose PTX did not show any differences from control with regard to RSG Cmax and AUC parameters. The time to peak concentration (tmax) of RSG was significantly increased in rats pretreated with PTX under both single- and multiple-dose conditions, whereas the elimination half-life (t1/2) of RSG was increased only with multiple-dose PTX pretreatment. In conclusion, the presence of PTX was found to cause a slight decrease in the oral exposure of RSG in rats. Concurrent use of PTX with RSG therefore needs to be appropriately evaluated for proper dose adjustments in humans.
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