Tirilazad Phenytoin

Fleishaker JC, Pearson LK, Peters GR. Induction of tirilazad clearance by phenytoin. Biopharm Drug Dispos 1998 19 91 96. 

Phenobarbital and phenytoin reduce the serum levels of tirilazad mesilate whereas ketoconazole increases them. Finasteride inhibits the metabolism of tirilazad to its active metabolite. No pharmacokinetic interaction appears to occur between cimetidine or nimodipine and tirilazad. 

After taking phenytoin 200 mg every 8 hours for 11 doses then 100 mg every 8 hours for 5 doses, the AUCg.g of tirilazad mesilate was reduced by 35% in 12 healthy subjects. The AUC of the active metabolite, U-89678, was reduced by 87%. Another report by the same group of workers found that phenytoin every 8 hours for 7 days (9 doses of200 mg followed by 13 doses of 100 mg) reduced the clearance of tirilazad by 92% and of U-89678 by 93%. In another report the authors noted that phenytoin increased the metabolism of tirilazad and its metabolite in men and women to similar extents. The clinical importance of these reductions is still to be assessed, but be alert for any evidence of reduced tirilazad effects if both drugs are given. 

Fleishaker JC, Hulst LK, Peters GR The effect of phenytoin on the pharmacc4cinetics of tirilazad mesylate in healthy male volunteers Clin Pharmacol Ther (19 ) 56,389-97... 

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See also in sourсe #XX -- [ ]

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