Pharmacokinetics and Clinical Use of Parenteral Phenytoin, Phenobarbital, and Paraldehyde

  title={Pharmacokinetics and Clinical Use of Parenteral Phenytoin, Phenobarbital, and Paraldehyde},
  author={Richard E. Ramsay},
  • R. Ramsay
  • Published 1 June 1989
  • Medicine, Biology
  • Epilepsia
Summary: Intravenous phenytoin, phenobarbital, and paraldehyde are effective and safe for the treatment of acute seizures such as status epilepticus. All of these drugs should be infused in a diluted solution and at a slow rate to minimize the occurrence of adverse effects. 
Intramuscular use of fosphenytoin
Investigations demonstrated that fosphenytoin is rapidly and completely absorbed after injection into muscle and is quickly converted to produce therapeutic phenytoin plasma concentrations within 30 min of administration, and was well tolerated both locally and systemically.
Parenteral antiepileptic/anticonvulsant drugs
Several benzodiazepines have been used as adjunctive drugs for the treatment of epilepsy; given parenterally, they provide rapid CNS entry and prompt control of seizures, but their effect is short lived.
Emergency Management of Seizures: An Overview
Phenytoin prodrug (ACC‐9653), an investigational new drug, is promptly absorbed after intramuscular injection and appears to be close to an ideal drug for the emergency management of seizures.
Emergency treatment of status epilepticus
Fosphenytoin, a prodrug and phosphate ester of phenytoin was developed to overcome the drawbacks associated with IV pheny toin and is a valuable option for the treatment of status epilepticus.
Safety and tolerance of multiple doses of intramuscular fosphenytoin substituted for oral phenytoin in epilepsy or neurosurgery.
Intramuscular fosphenytoin is a safe and well-tolerated alternative to oral phenytoin when oral administration is not feasible and oral phenYtoin therapy is resumed.
Guidelines for nonemergency use of parenteral phenytoin products: proceedings of an expert panel consensus process. Panel on Nonemergency Use of Parenteral Phenytoin Products.
This document summarizes the proceedings of an expert panel consensus process addressing the nonemergency use of parenteral phenytoin products for management of seizures in pediatric and adult
Effects of paraldehyde on the convulsions induced by administration of soman in rats
Co‐administration of paraldehyde and atropine sulfate might constitute a valuable tool to be used against the convulsant consequences of soman poisoning, but supplementary pre‐medication remains necessary to improve the antilethal capacity of the pre‐treatment.
Novel anesthetics and other treatment strategies for refractory status epilepticus
Refractory status epilepticus (RSE)-that is, seizures resistant to at least two antiepileptic drugs (AEDs)-is generally managed with barbiturates, propofol, or midazolam, despite a low level of evidence, and the need for alternative pharmacologic and nonpharmacologic strategies emerges.
Practical management of therapeutic diphenylhydantoin concentrations in children.
Therapeutic DPH concentration profiles can be managed satisfactorily in children in individual-specific DPH pharmacokinetic parameters derived and skillfully applied.


Paraldehyde therapy in childhood status epilepticus.
The results indicated no significant complications in patients who did not receive an initial IV bolus for status epilepticus and even though treatment with phenobarbital or diazepam and phenytoin sodium had failed, 37% had a good therapeutic response.
Intravenous phenytoin in acute treatment of seizures
Large doses of phenytoin were administered on 159 occasions to 139 adult patients who had had more than three seizures or were in status epilepticus and could be divided into two groups based on response to treatment.
High intravenous phenytoin dosage requirement in a newborn infant
The changing pharmacokinetics were attributed to maturation of oxidative metabolism of phenytoin, concurrent phenobarbital administration, or both, and the need for additional loading doses and maintenance dose increases must be guided by serum concentration measurements.
Use of parenteral diphenylhydantoin (dilantin) sodium in control of status epilepticus.
  • C. H. Carter
  • Medicine, Psychology
    A.M.A. archives of neurology and psychiatry
  • 1958
The parenteral use of diphenylhydantoin (Dilantin) sodium in the control of seizures was first described by Murphy and Schwab,1 of the Massachusetts General Hospital, in 1956, and pointed out the danger of using phenobarbital sodium intravenously or intramuscularly to suppress convulsions because of its severe depressant effect on respiration.
Brain uptake of phenytoin, phenobarbital, and diazepam.
The treatment of status epilepticus as indicated by the drug kinetics would be (1) initial use of IV diazepam to effect immediate seizure control due to more rapid penetration into the brain; and (2) subsequent rapid use ofIV phenytoin or phenobarbital to maintain seizure Control due to relative slow clearance of these drugs out of the brain, whilediazepam has a quite rapid clearance.
A method for shifting from oral to intramuscular diphenylhydantoin administration
There is a profound fall in plasma DPH levels and urinary 5‐(p‐hydroxyphenyl)‐5‐ phenylhydantoin (HPPH) excretion after intramuscular (IM) administration and that this fall is followed by significant rebound when oral administration is resumed.
In the practice of neurosurgical operations the convulsions occasionally elicited during cortical manipulations produced by electrical stimulations sometimes be difficult to control, and may give
Use of diphenylhydantoin.
An excellent summary of the clinical pharmacology of diphenylhydantoin by Easton (Ann Intern Med77:421-423, 1972) unfortunately emphasizes the concept of "dilantinization" w...
Efficacy of intravenous phenytoin in the treatment of status epilepticus: Kinetics of central nervous system penetration
Intravenous phenytoin rapidly enters the central nervous system and results in prompt and effective treatment of status epilepticus without suppressing higher cortical function or cardiorespiratory centers.
Sudden death following intravenous sodium diphenylhydantoin.