[(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)methoxy]phosphonic acid

• ChemBase ID: 1155
• Molecular Formular: C16H15N2O6P
• Molecular Mass: 362.273861
• Monoisotopic Mass: 362.06677284
• SMILES: P(=O)(OCN1C(=O)C(NC1=O)(c1ccccc1)c1ccccc1)(O)O
• Canonical SMILES: O=C1N(COP(=O)(O)O)C(=O)NC1(c1ccccc1)c1ccccc1
• 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)
• InChIKey: XWLUWCNOOVRFPX-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: [(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)methoxy]phosphonic acid
• IUPAC Traditional name: fosphenytoin
• Brand Name: Prodilantin; Cerebyx
• Synonyms: Fosphenytoin sodium; (3-Phosphoryloxymethyl)phenytoin; Fosfenitoina [inn-spanish]; Fosphenytoine [inn-french]; Fosphenytoinum [inn-latin]; Fosphenytoin

Database IDs

• CAS Number: 93390-81-9
• PubChem SID: 160964618; 46505168
• PubChem CID: 56339

CALCULATED PROPERTIES

JChem

• Acid pKa: 1.460733
• H Acceptors: 5
• H Donor: 3
• LogD (pH = 5.5): -0.8092683
• LogD (pH = 7.4): -2.7032614
• Log P: 1.6680293
• Molar Refractivity: 87.0537 cm^3
• Polarizability: 33.973347 Å^3
• Polar Surface Area: 116.17 Å^2
• Rotatable Bonds: 5
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.08
• LOG S: -3.4
• Solubility (Water): 1.45e-01 g/l

DETAILS

DrugBank - DB01320

• Drug Groups: approved
• Description: Fosphenytoin is a water-soluble phenytoin prodrug used only in hospitals for the treatment of epileptic seizures. It works by slowing down impulses in the brain that cause seizures. Its main mechanism is to block frequency-dependent, use-dependent and voltage-dependent neuronal sodium channels, and therefore limit repetitive firing of action potentials.
• Indication: For the control of generalized convulsive status epilepticus and prevention and treatment of seizures occurring during neurosurgery. It can also be substituted, short-term, for oral phenytoin.
• Pharmacology: Fosphenytoin is a water-soluble phenytoin prodrug used only in hospitals for the treatment of epileptic seizures. Following parenteral administration of fosphenytoin, fosphenytoin is converted to the anticonvulsant phenytoin by endogenous phosphatases. For every mmol of fosphenytoin administered, one mmol of phenytoin is produced. The pharmacological and toxicological effects of fosphenytoin include those of phenytoin.
• Toxicity: Nausea, vomiting, lethargy, tachycardia, bradycardia, asystole, cardiac arrest, hypotension, syncope, hypocalcemia, metabolic acidosis, and death have been reported in cases of overdosage with fosphenytoin. The median lethal dose of fosphenytoin given intravenously in mice and rats was 156 mg PE/kg and approximately 250 mg PE/kg, or about 0.6 and 2 times, respectively, the maximum human loading dose on a mg/m2 basis. Signs of acute toxicity in animals included ataxia, labored breathing, ptosis, and hypoactivity.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic.
• Absorption: Fosphenytoin is completely bioavailable following lM administration.
• Half Life: Fosphenytoin has a half-life of approximately 15 minutes.
• Protein Binding: Extensively bound (95% to 99%) to human plasma proteins, primarily albumin.
• Elimination: Phenytoin derived from administration of Cerebyx is extensively metabolized in the liver and excreted in urine primarily as 5-(p-hydroxyphenyl)-5-phenylhydantoin and its glucuronide; little unchanged phenytoin (1%–5% of the Cerebyx dose) is recovered in urine.
• Distribution: * 4.3 to 10.8 L
• References: Johnson J, Wrenn K: Inappropriate fosphenytoin use in the ED. Am J Emerg Med. 2001 Jul;19(4):293-4. [Pubmed] ; Applebaum J, Levine J, Belmaker RH: Intravenous fosphenytoin in acute mania. J Clin Psychiatry. 2003 Apr;64(4):408-9. [Pubmed] ; McCleane GJ: Intravenous infusion of fosphenytoin produces prolonged pain relief: a case report. J Pain. 2002 Apr;3(2):156-8. [Pubmed] ; Browne TR, Kugler AR, Eldon MA: Pharmacology and pharmacokinetics of fosphenytoin. Neurology. 1996 Jun;46(6 Suppl 1):S3-7. [Pubmed] ; Luszczki JJ: Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions. Pharmacol Rep. 2009 Mar-Apr;61(2):197-216. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

REFERENCES

• Johnson J, Wrenn K: Inappropriate fosphenytoin use in the ED. Am J Emerg Med. 2001 Jul;19(4):293-4. Pubmed
• Applebaum J, Levine J, Belmaker RH: Intravenous fosphenytoin in acute mania. J Clin Psychiatry. 2003 Apr;64(4):408-9. Pubmed
• McCleane GJ: Intravenous infusion of fosphenytoin produces prolonged pain relief: a case report. J Pain. 2002 Apr;3(2):156-8. Pubmed
• Browne TR, Kugler AR, Eldon MA: Pharmacology and pharmacokinetics of fosphenytoin. Neurology. 1996 Jun;46(6 Suppl 1):S3-7. Pubmed
• Luszczki JJ: Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions. Pharmacol Rep. 2009 Mar-Apr;61(2):197-216. Pubmed