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Fosphenytoin



Fosphenytoin
Systematic (IUPAC) name
(2,5-dioxo-4,4-diphenyl-imidazolidin-1-yl)methoxyphosphonic acid
Identifiers
CAS number 93390-81-9
ATC code N03AB05
PubChem 56339
DrugBank APRD00241
Chemical data
Formula C16H15N2O6P 
Mol. mass 362.274 g/mol
Pharmacokinetic data
Bioavailability 100% (IM)
Protein binding 95 to 99%
Metabolism Hepatic
Half life 15 minutes to convert to phenytoin
Excretion Renal (as phenytoin)
Therapeutic considerations
Pregnancy cat.

D(US)

Legal status

Prescription only

Routes Intravenous, intramuscular

Fosphenytoin (Cerebyx®, Parke-Davis; Prodilantin®, Pfizer Holding France[1]) is a water-soluble phenytoin prodrug used only in hospitals for the treatment of epileptic seizures.

On 18 November 2004, Sicor (a subsidiary of Teva) received a tentative approval letter from the United States Food and Drug Administration for a generic version of fosphenytoin.[2]

Additional recommended knowledge

Contents

Uses

Approved

Fosphenytoin is approved in the United States for the short term (five days or less) treatment of epilepsy when more widely used means of phenytoin administration are not possible or are ill-advised,[3] such as endotracheal intubation, status epilepticus or some other type of repeated seizures; vomiting, and/or the patient is unalert or not awake or both.[4]

Unapproved/off-label/investigational

In April of 2003, Applebaum and colleagues at the Ben-Gurion University of the Negev in Beersheba reported that even though anticonvulsants are often very effective in mania, and acute mania requires rapid treatment, fosphenytoin had no antimanic effect even 60 minutes after administration of doses used in status epilepticus.[5]

Fosphenytoin was more successfully used to relieve pain refractory to opiates in a 37-year-old woman with neuroma, according to Dr. Gary J. McCleane of the Rampark Pain Center in Lurgan, Northern Ireland.[6] She was given 1,500 phenytoin equivalent units of fosphenytoin over a 24 hour period, producing pain relief that last three to fourteen weeks after each infusion, allowing her to use less opiates.[6]

Metabolism

One mmol (millimole) of phenytoin is produced for every mmol of fosphenytoin administered; the hydrolysis of fosphenytoin also yields phosphate and formaldehyde, the latter of which is subsequently metabolized to formate, which is in turn metabolized by a folate dependent mechanism.[3]

Side effects

Side effects are similar to phenytoin, except that fosphenytoin causes less hypotension and more paresthesia.[7] Fosphenytoin can cause hyperphosphatemia in end-stage renal failure patients.[8]

History

Phenytoin, in both its acidic and sodium salt forms, is erratically bioavailable whether it is injected or taken orally due to its high melting point, weak acidity, and its being only sparingly soluble in water.[9] Simply putting patients on other drugs is not always an option; this was especially true before 1993, when the number of anticonvulsants available was much more limited.[10] One solution was to develop a prodrug that did not have these drawbacks.

Fosphenytoin was approved by the Food and Drug Administration (FDA) on August 5, 1996 for use in epilepsy.[11]

Notes and references

  1. ^ PRODILANTIN 75 mg/ml sol inj IM et p perf IV. VIDAL, l'information de référence sur les produits de santé. Retrieved on 23 October, 2005.
  2. ^ Fosphenytoin Sodium Approval History. Retrieved on 20 October, 2005.
  3. ^ a b Parke-Davis (2001). Cerebyx®: Fosphenytoin Sodium Injection - Labeling Revision (PDF). Cerebyx Approval History. Warner-Lambert Company. Retrieved on 20 October, 2005.
  4. ^ Johnson J, Wrenn K (2001). "Inappropriate fosphenytoin use in the ED". American Journal of Emergency Medicine 19 (4): 293-4. PMID 11447516. Fulltext options List of Library Holdings Worldwide
  5. ^ Applebaum J, Levine J, Belmaker RH (2003). "Intravenous fosphenytoin in acute mania" (PDF). Journal Clinical Psychiatry 64 (4): 408-9. PMID 12716241.
  6. ^ a b McCleane GJ (2002). "Intravenous infusion of fosphenytoin produces prolonged pain relief: a case report". The Journal of Pain 3 (2): 156-8. PMID 14622802. List of Library Holdings Worldwide
  7. ^ Browne TR. (1997). "Fosphenytoin (Cerebyx)". Clinical Neuropharmacology 20 (1): 1-12. PMID 9037568. List of Library Holdings Worldwide
  8. ^ McBryde KD, Wilcox J, Kher KK (2005). "Hyperphosphatemia due to fosphenytoin in a pediatric ESRD patient" (PDF). Pediatric Nephrology (Berlin, Germany) 20 (8): 1182-5. PMID 15965770.
  9. ^ Yamaoka Y, Roberts RD, Stella VJ. "Low-melting phenytoin prodrugs as alternative oral delivery modes for phenytoin: a model for other high-melting sparingly water-soluble drugs." Journal of Pharmaceutical Science. 1983 Apr;72(4):400-5. PMID 6864479
  10. ^ Anticonvulsants before 1993 Neuroland
  11. ^ Cerebyx Approval History. Retrieved on 20 October, 2005.

See also

 
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Fosphenytoin". A list of authors is available in Wikipedia.
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