Because phenytoin is hydroxylated in the liver by an enzyme system which is saturable at high plasma levels small incremental doses may increase the half-life and produce very substantial increases in serum levels, when these are in the upper range. Clinical studies wshow that chewed and unchewed phenytoin infatabs are bioequivalent, yield approximately equivalent plasma levels, and are more rapidly absorbed than 100-mg phenytoin kapseals. The plasma half-life in man after IV administration ranges from 10 to 15 hours. A fall in plasma levels may occur when patients are changed from oral to IM administration. The drop is caused by slower absorption, as compared to oral administration, due to poor water solubility of phenytoin.
IV administration is the preferred route for producing therapeutic serum levels.
There are occasions when IM administration may be required, i.e. postoperatively, in comatose patients, for GI upsets. During these periods, a sufficient dose must be administered intramuscularly to maintain the plasma level within the therapeutic range. Where oral dosage is resumed following IM usage, the oral dose should be properly adjusted to compensate for the wslow continuing IM absorption to avoid toxic syndromes. Patients stabilized on a daily oral regimen of phenytoin experience a drop in peak blood levels to 50-60 percent of stable levels if crossed over to an equal dose administered intramuscularly. Experience for periods greater than one week is lacking and blood level monitoring is recommended.