The effect of administration of phenytoin on the pharmacokinetics of isoxicam.

This study was designed to determine whether the disposition of isoxicam is influenced by the coadministration of another acidic drug, highly bound to plasma proteins and extensively metabolized, i.e., phenytoin. Ten healthy volunteers received an oral dose of 200 mg of isoxicam prior to and following the oral administration of phenytoin (100 mg) twice a day for 10 days. Eleven blood samples were drawn during the period following each dose of isoxicam. The area under the isoxicam plasma concentration-time curve (AUC infinity) increased from 389 +/- 66 to 464 +/- 62 micrograms h ml-1 (+/- SEM) (p less than 0.05) after treatment with phenytoin. This increase was due to an increase in isoxicam bioavailability; the absorption rate constant for isoxicam increased correspondingly from 0.34 +/- 0.06 to 1.16 +/- 0.38 h-1 (p less than 0.05). Distribution and clearance of isoxicam were probably not affected as its half-life was not changed, its plasma peak concentration increased, and the time to reach this peak decreased. It is concluded that phenytoin increases the rate and extent of absorption of isoxicam.