The Experts below are selected from a list of 33 Experts worldwide ranked by ideXlab platform

Diane A Enezra - One of the best experts on this subject based on the ideXlab platform.

  • safety of Fosphenytoin Sodium
    American Journal of Health-system Pharmacy, 1996
    Co-Authors: Lesley Fierro, Donna Savulich, Diane A Enezra
    Abstract:

    Fosphenytoin Sodium is reviewed, and its safety is compared with that of phenytoin. After i.v. or i.m. injection, Fosphenytoin, a phenytoin prodrug, is rapidly hydrolyzed to phenytoin. Free-phenytoin concentrations equivalent to those obtained with i.v. phenytoin can be achieved with Fosphenytoin given at equimolar loading doses by selecting the appropriate rate of Fosphenytoin administration. Fosphenytoin can be expected to interact with the same drugs that interact with phenytoin. The dosage is expressed as phenytoin Sodium equivalents (PE). The standard loading dose for adults with status epilepticus is 15-20 mg PE/kg i.v. infused at 100-150 mg/min; i.m. administration is not recommended for this condition. For nonemergency situations, a 10- to 20-mg PE/kg loading dose can be given i.v. or i.m. Fosphenytoin has advantages over phenytoin injection that are related to its greater aqueous solubility, which obviates the extreme alkalinity, propylene glycol, and ethanol needed in the injectable phenytoin formulation. Intravenous Fosphenytoin has been associated with less soft-tissue injury and fewer adverse effects in general than phenytoin. Fosphenytoin, when administered i.m., is completely absorbed, is relatively well tolerated, and provides more predictable serum drug concentrations than i.m. phenytoin. Fosphenytoin offers practical and clinical advantages over i.v. phenytoin.

Yuji Kumagai - One of the best experts on this subject based on the ideXlab platform.

Curtis E Haas - One of the best experts on this subject based on the ideXlab platform.

  • relative bioavailability of orally administered Fosphenytoin Sodium injection compared with phenytoin Sodium injection in healthy volunteers
    Pharmacotherapy, 2015
    Co-Authors: Kevi A Kauche, Nicole M Acquisto, Gauri G Rao, David C Kaufma, Jeff Huntress, Ala Forres, Curtis E Haas
    Abstract:

    tudy Objective To describe the pharmacokinetics of Fosphenytoin (FPHT) Sodium injection when administered orally, and to determine the relative oral bioavailability (FREL) of FPHT Sodium injection compared with PHT Sodium injection based on pharmacokinetic modeling in healthy volunteers. Design Open-label, randomized, single-dose, two-period, two-sequence crossover study. Setting University-affiliated clinical research center funded by the National Center of Research Resources. Subjects Ten healthy adult volunteers. Intervention Subjects were randomized to receive a single oral dose of either PHT Sodium injection or FPHT Sodium injection at a dose equivalent to 400 mg PHT acid. Blood samples were collected at baseline (just prior to administration) and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after dose administration. After a 7–14-day washout period, the subjects underwent the same study procedures for administration of the other agent (PHT or FPHT). Measurements and Main Results The mean age and weight of the 10 subjects were 37 years and 72.5 kg, respectively, and the mean dose was 5.6 mg/kg based on PHT acid equivalence. The mean FREL of FPHT was 1.21 (95% confidence interval [CI] 1.07–1.35). Serum PHT concentrations were determined by fluorescence polarization immunoassay. The median (range) maximum serum concentration (Cmax) values were significantly higher after FPHT administration compared with PHT: 10.7 (9.0–19.4) mg/L versus 5.0 (3.2–8.9) mg/L (p=0.002). The PHT concentration after oral administration of FPHT displayed faster absorption compared with PHT, with a median (range) time to reach Cmax of 1.0 (0.5–2.0) hours versus 6.0 (2.0–24.0) hours (p=0.008). All subjects completed the study without any serious adverse events reported. Conclusion FPHT Sodium injection given orally was absorbed more rapidly and to a significantly greater extent than PHT Sodium injection given orally to healthy volunteers. Further evaluation of oral FPHT as an alternative in patients requiring enteral feedings is warranted.

Lesley Fierro - One of the best experts on this subject based on the ideXlab platform.

  • safety of Fosphenytoin Sodium
    American Journal of Health-system Pharmacy, 1996
    Co-Authors: Lesley Fierro, Donna Savulich, Diane A Enezra
    Abstract:

    Fosphenytoin Sodium is reviewed, and its safety is compared with that of phenytoin. After i.v. or i.m. injection, Fosphenytoin, a phenytoin prodrug, is rapidly hydrolyzed to phenytoin. Free-phenytoin concentrations equivalent to those obtained with i.v. phenytoin can be achieved with Fosphenytoin given at equimolar loading doses by selecting the appropriate rate of Fosphenytoin administration. Fosphenytoin can be expected to interact with the same drugs that interact with phenytoin. The dosage is expressed as phenytoin Sodium equivalents (PE). The standard loading dose for adults with status epilepticus is 15-20 mg PE/kg i.v. infused at 100-150 mg/min; i.m. administration is not recommended for this condition. For nonemergency situations, a 10- to 20-mg PE/kg loading dose can be given i.v. or i.m. Fosphenytoin has advantages over phenytoin injection that are related to its greater aqueous solubility, which obviates the extreme alkalinity, propylene glycol, and ethanol needed in the injectable phenytoin formulation. Intravenous Fosphenytoin has been associated with less soft-tissue injury and fewer adverse effects in general than phenytoin. Fosphenytoin, when administered i.m., is completely absorbed, is relatively well tolerated, and provides more predictable serum drug concentrations than i.m. phenytoin. Fosphenytoin offers practical and clinical advantages over i.v. phenytoin.

A R Kugle - One of the best experts on this subject based on the ideXlab platform.

  • safety and tolerance of multiple doses of intramuscular Fosphenytoin substituted for oral phenytoin in epilepsy or neurosurgery
    JAMA Neurology, 1996
    Co-Authors: J Wilde, K Campbell, R E Ramsay, William R Garne, John M Pellock, S A Henki, A R Kugle
    Abstract:

    Background: Safety, tolerability, and pharmacokinetics of Fosphenytoin Sodium, a water-soluble phenytoin prodrug, were investigated after a temporary substitution of intramuscular Fosphenytoin for oral phenytoin Sodium in 240 epileptic or neurosurgical patients taking oral phenytoin Sodium (100-500 mg/d). Methods: Patients were randomly assigned to 1 of 2 parallel groups. During screening and follow-up, patients were maintained on a regimen of oral phenytoin at an individualized dose. During treatment, the phenytoin-treated patients received intramuscular placebo and their prescribed dose of oral phenytoin; the Fosphenytoin-treated patients received oral placebo and intramuscular Fosphenytoin equimolar to their phenytoin dose. Results: Both groups had similar types and frequencies of mild to moderate adverse events. Fosphenytoin was as well tolerated as intramuscular placebo at the injection site. Intramuscular Fosphenytoin equimolar to a patient's oral phenytoin dose produced equal or greater plasma phenytoin concentrations. Conclusions: Dosing adjustments are not required when intramuscular Fosphenytoin is temporarily substituted or oral phenytoin therapy is resumed. Intramuscular Fosphenytoin is a safe and well-tolerated alternative to oral phenytoin when oral administration is not feasible.

  • pharmacology and pharmacokinetics of Fosphenytoin
    Neurology, 1996
    Co-Authors: Thomas R Owne, A R Kugle, Michael A Eldo
    Abstract:

    Fosphenytoin Sodium, a phosphate ester prodrug of phenytoin, was developed as a replacement for parenteral phenytoin Sodium.Unlike phenytoin, Fosphenytoin is freely soluble in aqueous solutions, including standard IV solutions, and is rapidly absorbed by the IM route. Fosphenytoin is metabolized (conversion half-life of 8 to 15 min) to phenytoin by endogenous phosphatases. Therapeutic free (unbound) and total plasma phenytoin concentrations are consistently attained after IM or IV administration of Fosphenytoin loading doses. Fosphenytoin has fewer local adverse effects (e.g., pain, burning, and itching at the injection site) after IM or IV administration than parenteral phenytoin. Systemic effects related to the CNS are similar for both preparations, but transient paresthesias are more common with Fosphenytoin. NEUROLOGY 1996;46(Suppl 1): S3-S7