Abstracts

Rationale: Intravenous (IV) loading dose (LD) of Dilantin (PHT) or Fosphenytoin (FOS) is used for either acute seizure management or its prophylaxis with a recommended LD of PHT/FOS based on indication ranging from 15 to 30 mg/kg. When treating seizures, targeted total serum PHT (tPHT) level is between 20 and 30 mcg/mL, but aimed for non-toxic range when used for seizure prophylaxis. The timing of PHT/FOS maintenance initiation is variable. We investigated a correlation between a single weight-based PHT/FOS loading without subsequent maintenance doses and post-infusion serum PHT levels obtained within first 24 hoursMethods: Retrospective single academic medical center chart review over 4-year period identified 86 PHT-naive patients who received a single LD of PHT/FOS Phenytoin equivalents (PE) of >=500 mg and noted the tPHT level obtained within next 24 hours. Whenever available, free PHT (fPHT) level was included. Serum PHT levels were correlated with the LD. The relationship between total and free serum PHT levels was studiedResults: Of the 86 patients, the weight-based LD of PHT/FOS ranged between 3.9 and 27.08 mg/kg (average 18.99 mg/kg). 30 (34.88%) had serum tPHT level >=20 mcg/mL (LD range 15.0-27.1 mg/kg). In 21 with corresponding fPHT levels, 16 (64%) had level >= 2.0. 56 patients had tPHT serum level of < 20 mg/ml (LD range 3.9-25.4 mg/kg). In 33 with corresponding fPHT levels, 26 (78.79 %) had level < 2.0. Among 55 patients receiving a LD between 10 and 19 mg/ kg, 37 (67.27%) had tPHT level <20 mcg/mL. In 38 with corresponding free levels, 21 (55.26%) had fPHT level < 2.0. Among 30 patients who received a LD >=20 mg/kg, only 12 (40%) had total level of >=20 mcg/mL. In 15 with corresponding fPHT level, only 6 (40 %) had levels of >=2.0. Among 51 with concomitant free and total PHT serum levels, we calculated the percent of free fraction from total PHT level. On average the fPHT level correlated to about 12 % of tPHT, but ranged between 5 and 27%.Conclusions: Weight-based LD of PHT/FOS is aimed to attain high or supra-therapeutic serum levels of PHT in the initial phase and possibly in the first 24 hours of acute seizure management to ensure timely seizure cessation and prevention of seizure recurrence. In our cohort tPHT serum level of >=20 mcg/mL following a single LD of >= 20 mg/kg was noted in only 40% of patients when checked during subsequent 24 hours. Moreover, even among those patients who had LD of <20 mg/kg, 32.73% had serum tPHT level >20 mcg/mL. These observations confirm that the PHT dosing is complex and suggest that in addition to calculating adequate LD, maintenance doses of PHT/FOS may need to be initiated within first 24 hours if continued sufficient serum PHT levels are required. Lastly, wide variability in percent correlation between the total and unbound pharmacologically active fPHT fraction raises concern that total PHT level is an inaccurate measure potentially leading to either under-treatment (which may be detrimental in case of recurrent seizures) or over-treatment (leading to medication toxicity). Free PHT serum level is a preferred measure of drug monitoring