PHARMACOLOGY AND PHARMACOKINETICS OF FOSPHENYTOIN

Fosphenytoin sodium, a phosphate ester prodrug of phenytoin, was devel oped as a replacement for parenteral phenytoin sodium. Unlike phenytoi n, fosphenytoin is freely soluble in aqueous solutions, including stan dard IV solutions, and is rapidly absorbed by the IM route. Fosphenyto in is metabolized (conversion half-life of 8 to 15 min) to phenytoin b y endogenous phosphatases. Therapeutic free (unbound) and total plasma phenytoin concentrations are consistently attained after IM or IV adm inistration of fosphenytoin loading doses. Fosphenytoin has fewer loca l adverse effects (e.g., pain, burning, and itching at the injection s ite) after IM or IV administration than parenteral phenytoin. Systemic effects related to the CNS are similar for both preparations, but tra nsient paresthesias are more common with fosphenytoin.