Fosphenytoin: Pharmacokinetics and tolerance of intramuscular loading doses

Purpose: Fosphenytoin (FPHT; Cerebyx) is well absorbed when given intramusc ularly (IM). All prior pharmacokinetic studies had the first plasma sample obtained 30 min after IM administration. The objectives of this study were to determine the rate and extent of FPHT absorption and to evaluate the tol erability of IM FPHT compared with IM saline. Methods: This was an open-label, double-blinded study in which patients rec eived 10 mg/kg dose of IM FPHT in one gluteus and IM saline in the other gl uteus. Half the patients received saline injection of equal volume to FPHT (up to 19.5 mL); the other half received 2 mL of saline. Neurologic examina tion, vital signs, PHT blood samples. injection site examination, and subje ctive pain scores at injection site were obtained before and at timed inter vals for 6 h. Results. Total PHT serum concentrations 10 mug/mL were obtained in 5 min in 14.3% of patients and in 26.3% after 10 min. More than half the patients h ad therapeutic serum concentrations at 30 min; 45.8% of patients reported n o pain at either the FPHT or saline injection site. No significant differen ce in pain was noted between FPHT and saline injection sites at 60 min and thereafter. Early decrease in blood pressure occurred but was not clinicall y significant. Classic PHT-induced central nervous system (CNS) side effect s were evident in one third of patients within 1 h after injection, Conclusions: (a) LM FPHT is rapidly absorbed (therapeutic levels achieved a s early as 5-20 min). (b) IM FPHT is well tolerated by most patients irresp ective of injection volume.