Fosphenytoin sodium, the sodium salt form of fosphenytoin, is a prodrug of phenytoin with similar anticonvulsant properties. It is intended for parenteral administration; As a prodrug, it is hydrolyzed to the phenytoin,which is the active metabolite. Phenytoin exerts its effect most likely through an enhancement of sodium efflux from neurons in the motor cortex. This leads to a suppression of excessive neuronal firing and spread of seizure activity. Other physiologic effects from actions of phenytoin include modulation of the voltage-dependent calcium channels of neurons, inhibition of calcium flux across neuronal membranes and enhancement of sodium-potassium ATPase activity of neurons and glial cells.

Physicochemical Properties

Molecular Formula	C16H15N2NAO6P
Molecular Weight	385.263635873795
Exact Mass	406.031
CAS #	92134-98-0
Related CAS #	Fosphenytoin;93390-81-9;Fosphenytoin-d10 disodium
PubChem CID	56338
Appearance	White to off-white solid powder
Melting Point	220ºC
LogP	2.691
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	27
Complexity	536
Defined Atom Stereocenter Count	0
InChi Key	GQPXYJNXTAFDLT-UHFFFAOYSA-L
InChi Code	InChI=1S/C16H15N2O6P.2Na/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);;/q;2*+1/p-2
Chemical Name	disodium;(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)methyl phosphate
Synonyms	Cerebyx; Pro-Epanutin; HMPDP; ACC-9653; ACC-9653; ACC9653; Fosphenytoin Sodium; Prodilantin
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	Voltage-dependent neuronal sodium (Na+) channel blocker (proposed primary mechanism for neuroprotection). [1]
ln Vivo	A powerful neuroprotective medication against damage brought on by ischemia is fosphenytoin. Hippocampal CA1 pyramidal neurons in rats given fosphenytoin (30 mg/kg, im) five minutes after the commencement of the ischemic episode stayed close to control levels (13.90 +/- 0.92), although there were no appreciable alterations in GFAP staining[1]. Rats given 84 mg/kg of fosphenytoin had an 83% relative bioavailability of the drug. In completely kindled female Wistar rats, fosphenytoin dose-dependently raises the focal seizure (post-discharge) threshold. Only after administering the largest dose of fosphenytoin tested (84 mg/kg) did seizure intensity and threshold duration decrease [2]. In a rat model of transient global ischemia induced by 12-minute cardiac arrest, a single intramuscular dose of Fosphenytoin Sodium (30 mg/kg) administered 5 minutes after resuscitation significantly reduced neuronal damage in the hippocampal CA1 region. Seven days post-ischemia, the number of normal-appearing CA1 pyramidal neurons in the treated group (13.90 ± 0.92 per 100 μm²) was nearly identical to sham-operated controls (14.33 ± 1.73) and significantly higher than in the saline-treated ischemic group (2.19 ± 0.16). [1] Despite its potent neuroprotective effect, post-ischemic treatment with Fosphenytoin Sodium did not significantly alter the increased glial fibrillary acidic protein (GFAP) immunoreactivity (a marker of astrocyte activation) observed in the hippocampal CA1 region 7 days after the ischemic insult. The optical density of GFAP staining in the CA1 region of the treated group (93.5 ± 0.71) was not significantly different from the saline-treated ischemic group (89 ± 9.9), but was significantly lower than the sham group (112 ± 3.54). [1]
Animal Protocol	Global Ischemia Model: Transient global ischemia was induced in male Long-Evans hooded rats (250-350 g) under ketamine anesthesia. A padded, weighted bar was lowered onto the chest for 12 minutes, causing cardiac arrest. Circulation was restored by cardiopulmonary resuscitation after the ischemic period. Brain temperature was monitored and maintained at 35 ± 0.4°C. [1] Drug Treatment: Animals were randomly assigned to groups. The treatment group received a single intramuscular injection of Fosphenytoin Sodium (30 mg/kg) in the right hind limb, administered 5 minutes after resuscitation. The control ischemic group received an intramuscular injection of saline at the same time point. Sham-operated animals underwent the same procedures except for chest compression. [1] Tissue Analysis: All animals were sacrificed 7 days post-ischemia. Brains were fixed, and the dorsal hippocampus was sectioned. For neuronal quantification, 1 μm thick plastic-embedded sections of the mid-CA1 region were stained with toluidine blue. Normal-appearing pyramidal neurons were counted blind in defined 100 μm² fields. For astrocyte assessment, 40 μm vibratome sections from the same region were processed for GFAP immunohistochemistry using a standard avidin-biotin-peroxidase method, and immunoreactivity was quantified by optical density analysis. [1]
ADME/Pharmacokinetics	Fosphenytoin Sodium is a water-soluble prodrug of phenytoin. In tissues and blood, it is rapidly converted by phosphatases to phenytoin, which is the active moiety. [1] It is suitable for intramuscular administration, with rapid absorption reported. [1]
Toxicity/Toxicokinetics	In this study, intramuscular administration of Fosphenytoin Sodium (30 mg/kg) did not cause significant local tissue irritation at the injection site in rats. [1] The literature cited within the article notes that Fosphenytoin Sodium offers a safety advantage over intravenous phenytoin, which can cause severe tissue irritation and venous complications. [1]
References	[1]. Fosphenytoin reduces hippocampal neuronal damage in rat following transient global ischemia. Acta Neurochir (Wien). 1998;140(2):175-80. [2]. Anticonvulsant effect of fosphenytoin in amygdala-kindled rats: comparison with phenytoin. Epilepsy Res. 1998 Mar;30(1):69-76.
Additional Infomation	Fosphenytoin Sodium is the sodium salt form of fosphenytoin, a prodrug that is hydrolyzed to the anticonvulsant phenytoin upon parental administration. Phenytoin exerts its effect most likely through an enhancement of sodium efflux from neurons in the motor cortex. This leads to a suppression of excessive neuronal firing and spread of seizure activity. Other physiologic effects from actions of phenytoin include modulation of the voltage-dependent calcium channels of neurons, inhibition of calcium flux across neuronal membranes and enhancement of sodium-potassium ATPase activity of neurons and glial cells. (NCI05) See also: Fosphenytoin (is salt form of). Fosphenytoin Sodium (Cerebyx®) is a disodium phosphate ester prodrug of the antiepileptic drug phenytoin. It was developed to overcome the solubility and tissue irritation issues associated with parenteral phenytoin formulation. [1] The proposed neuroprotective mechanism is primarily through its active metabolite, phenytoin, blocking voltage-dependent neuronal sodium channels. This may inhibit the cascade of events (Na+ influx, Ca2+ overload, glutamate release) leading to neuronal death following ischemia. [1] The study demonstrates a dissociation between neuronal protection and astrocyte GFAP response following Fosphenytoin Sodium treatment, suggesting that increased GFAP immunoreactivity post-ischemia may reflect astrocyte metabolic activation rather than solely indicating neuronal damage. [1]

Solubility Data

Solubility (In Vitro)	H2O : ≥ 100 mg/mL (~246.16 mM)
Solubility (In Vivo)	Solubility in Formulation 1: 25 mg/mL (61.54 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.5956 mL	12.9782 mL	25.9565 mL
	5 mM	0.5191 mL	2.5956 mL	5.1913 mL
	10 mM	0.2596 mL	1.2978 mL	2.5956 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.