Chemistry:Fosphenytoin

Short description: Anti-epileptic drug

Fosphenytoin

Clinical data
Trade names	Cerebyx, Pro-Epanutin
AHFS/Drugs.com	Monograph
MedlinePlus	a604036
License data	US DailyMed: Fosphenytoin
Pregnancy category	US: D (Evidence of risk)
Routes of administration	Intravenous, intramuscular
ATC code	N03AB05 (WHO)
Legal status
Legal status	US: ℞-only In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability	100% (IM)
Protein binding	95–99%
Metabolism	Liver
Elimination half-life	15 minutes to convert to phenytoin
Excretion	Kidney (as phenytoin)
Identifiers
IUPAC name (2,5-Dioxo-4,4-diphenyl-imidazolidin-1-yl)methoxyphosphonic acid
CAS Number	93390-81-9 Y
PubChem CID	56339
IUPHAR/BPS	7190
DrugBank	DB01320 Y
ChemSpider	50839 Y
UNII	B4SF212641
KEGG	D07993 Y
ChEMBL	ChEMBL919 N
Chemical and physical data
Formula	C16H15N2O6P
Molar mass	362.278 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C3N(C(=O)C(c1ccccc1)(c2ccccc2)N3)COP(=O)(O)O
InChI InChI=1S/C16H15N2O6P/c19-14-16(12-7-3-1-4-8-12,13-9-5-2-6-10-13)17-15(20)18(14)11-24-25(21,22)23/h1-10H,11H2,(H,17,20)(H2,21,22,23) Y Key:XWLUWCNOOVRFPX-UHFFFAOYSA-N Y
NY (what is this?)  (verify)

Fosphenytoin, also known as fosphenytoin sodium, and sold under the brand name Cerebyx among others, is a water-soluble phenytoin prodrug that is administered intravenously to deliver phenytoin, potentially more safely than intravenous phenytoin. It is used in the acute treatment of convulsive status epilepticus.

Fosphenytoin was developed in 1996. 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.

Medical uses

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

Other

In 2003, it was reported that even though anticonvulsants are often very effective in mania, and acute mania requires rapid treatment, fosphenytoin had no antimanic effect.

Metabolism

One millimole of phenytoin is produced for every millimole 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.

Side effects

Side effects are similar to intravenous phenytoin and include hypotension, cardiac arrhythmias, CNS adverse events (nystagmus, dizziness, sedation/somnolence, ataxia and stupor), and local dermatological reactions. Purple glove syndrome probably occurs with fosphenytoin but possibly at lower frequency than with intravenous phenytoin. Fosphenytoin can cause hyperphosphatemia in end-stage renal failure patients.

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. 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. 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.

See also

• Ethotoin
• Hydantoin
• Mephenytoin
• Phenytoin

External links

• "Fosphenytoin". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/fosphenytoin. 
• "Fosphenytoin sodium". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/fosphenytoin%20sodium.