Abstracts

Rationale: Objective: Prophylactic use of antiepileptic drugs is common in subarachnoid hemorrhage (SAH), and fosphenytoin is frequently used for the rapid delivery of phenytoin in SAH patients. The present study was performed to investigate the safety, tolerability, and pharmacokinetic profiles of rapid intravenous loading of fosphenytoin in SAH patients.Methods: Methods: Fosphenytoin was administered intravenously at a single loading dose of 20mg phenytoin-equivalent (PE)/kg with an infusion rate of 150mgPE/min to 30 adult patients with SAH, who experienced seizures or had a clinical suspicion of nonconvulsive seizure. Plasma concentrations of total phenytoin and free phenytoin were determined, and adverse events were assessed at 0, 10, 20 minutes and 24 hours after the infusion of fosphenytoin.Results: Results: Four patients experienced transient lowering of blood pressure, but other adverse events were not observed. All patients reached the therapeutic level of free phenytoin (1-2mg/L) at the end of infusion, but most patients (28/30) reached markedly supratherapeutic range with mean plasma concentration was 17.7±8.13mg/L, The higher plasma concentration maintained to 20 minutes after infusion (mean concentration; 3.46±3.75mg/L). At 24 hours after loading, a majority of patients (25/30) maintained within therapeutic range of free phenytoin.Conclusions: Conclusion: Rapid intravenous loading of fosphenytoin is well tolerated and effective in prompt achieving the therapeutic level of free phenytoin, but most patients experienced overshoot of free phenytoin at the end of infusion. Because increased plasma concentrations may increase the risk for cardiovascular complication, additional studies would be needed to find out the optimal dose and infusion rate of fosphenytoin in SAH patients.