Enhanced metabolism of mexiletine after phenytoin administration.
1 Unexpectedly low plasma concentrations of mexiletine were observed in three patients treated with mexiletine and concurrently taking phenytoin. 2 Six healthy volunteers were given a single oral dose of mexiletine (400 mg), before and after 1 week of phenytoin administration (300 mg/day). 3 The mean +/- s.d. area under the plasma mexiletine concentration-time curve decreased from 17.67 +/- 6.21 to 8.01 +/- 3.64 micrograms ml-1 h (P less than 0.003). 4 The mean +/- s.d. half-life of elimination of mexiletine decreased from 17.2 +/- 5.26 to 8.4 +/- 4.17 h (P less than 0.02) 5 The suggested mechanism of the interaction is hepatic mixed-function oxidase enzyme induction by phenytoin. 6 The interaction is likely to be clinically significant.
D000328:Adult; D001682:Biological Availability; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D008801:Mexiletine / Q000378:metabolism*; D010672:Phenytoin / Q000494:pharmacology*; D011437:Propylamines / Q000378:metabolism*
D011437:Propylamines; D008801:Mexiletine; D010672:Phenytoin