to albumin, and it has a very variable- dose dependent half-life. At therapeutic doses, the half-life can range from 8-60 hours, with an average of 20-30 hours, but in overdose situations, the half-life can increase to 24-230 hours. This dose dependent change helps to explain the delayed decrease in phenytoin levels seen in this patient. Phenytoin is metabolized in the liver by parahydroxylation by the CYP450 enzyme. This system becomes saturated at higher doses and turns into zero order kinetics, so while this patient was not on another drug that utilizes the P450 enzyme, this could be a factor in many other patients. Causes of extreme build-ups of phenytoin are hypoalbuminemia, hepatic dysfunction, hereditary insufficient parahydroxylation, and inhibition of metabolism by other drugs. There are many drugs that have been known to displace phenytoin from protein binding sites in the plasma. Of particular note is heparin. This is significant in the hospital setting due to the high numbers of patients in the hospital on heparin for DVT prophylaxis, including our patient. It took four days for the phenytoin levels to drop back to therapeutic values, which can be explained by the high initial phenytoin levels, the use of heparin for DVT prophylaxis, and the long absorption time from the gut. On discharge, the patient was switched to Lacosamide for seizure prophylaxis rather than phenytoin to prevent future adverse reactions.
32 J LA MED SOC | VOL 171 | NO. 1
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