The effect of administration of phenytoin on the pharmacokinetics of isoxicam

✍ Scribed by Dr G. Caillé; P. du Souich; L. Larivière; M. Vézina; Y. Lacasse

• Publisher: John Wiley and Sons
• Year: 1987
• Tongue: English
• Weight: 258 KB
• Volume: 8
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/bdd.2510080107

✦ Synopsis

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 200mg of isoxicam prior to and following the oral administration of phenytoin (100mg) 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 concentrationtime curve (AUC,) increased from 389 ? 66 to 464 ? 62 pg h ml-' (? SEM) (p < 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 k 0.38 h-l (p < 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.