Disease relevance of C07840

• With its efficacy, safety, and ease of administration, fosphenytoin is a valuable option for the treatment of status epilepticus [1].
• Systemic effects related to the CNS are similar for both preparations, but transient paresthesias are more common with fosphenytoin [2].
• Aside from local reactions, the most common adverse events associated with fosphenytoin have been pruritus and reactions typical of phenytoin (e.g., dizziness, somnolence, and ataxia) [3].
• Specimens were collected 2-120 h after fosphenytoin administration from 17 patients with renal insufficiency [4].
• METHODS: A single dose of fosphenytoin (250 mg over a period of 30 min) was administered to subjects with hepatic cirrhosis (n = 4), renal disease requiring maintenance hemodialysis (n = 4), and healthy controls (n = 4) [5].

High impact information on C07840

• Subtherapeutic free phenytoin levels following fosphenytoin therapy in status epilepticus [6].
• Studies of the pharmacokinetics, safety, and tolerance of i.v. fosphenytoin have demonstrated that fosphenytoin produces phenytoin plasma concentrations similar to those achieved with oral and i.v. phenytoin, but without significant cardiovascular effects and only minimal discomfort at the injection site [3].
• Pharmacology and pharmacokinetics of fosphenytoin [2].
• CONCLUSIONS: A unique immunoreactive oxymethylglucuronide metabolite derived from fosphenytoin has been isolated from sera from uremic patients receiving this prodrug [7].
• Glucuronidation of prodrug reactive site: isolation and characterization of oxymethylglucuronide metabolite of fosphenytoin [7].

Chemical compound and disease context of C07840

• Also studied was the role of uremic toxins hippuric acid and indoxyl sulfate as potential inhibitor of the protein binding of fosphenytoin because these compounds impair protein binding of phenytoin in uremia [8].
• The preferred treatment pathway for generalised convulsive status epilepticus (GCSE) is intravenous (i.v.) administration of 4 mg of lorazepam or 10 mg of diazepam directly followed by 15-18 mg/kg of phenytoin or equivalent fosphenytoin [9].
• During withdrawal of anaesthetic therapy, intravenous phenytoin/fosphenytoin or valproate should be continued (these agents having been administered during earlier phases of GCSE) to ensure an adequate baseline of antiepileptic medication so as to prevent the recurrence of status epilepticus [10].
• Benzodiazepines have become first-line drugs for treatment of acute seizures and status epilepticus, followed by phenytoin/fosphenytoin and phenobarbital [11].
• RESULTS: Patient 1 was admitted for subacute encephalopathy that was complicated by secondarily generalized status epilepticus resistant to lorazepam, fosphenytoin, and pentobarbital coma [12].

Biological context of C07840

• The relative bioavailability of fosphenytoin was 83% [13].
• In contrast, none caused any displacement of fosphenytoin from protein binding [8].
• Fosphenytoin is indicated for the treatment of generalized convulsions and seizures occurring during neurosurgery [14].
• The results show that hydrolysis of amino esters 8 is very fast, much more than that of fosphenytoin [15].
• In 4-week studies conducted in rats and dogs receiving fosphenytoin containing DPHA levels up to 1.1%, and in an in vitro structural chromosome aberration test with DPHA levels up to 2.0%, all findings were consistent with known effects of phenytoin (such as CNS signs and increased liver weight), and none were attributed to DPHA [16].

Anatomical context of C07840

• Thus, fosphenytoin showed anticonvulsant properties similar to phenytoin in amygdala kindled rats [13].
• A comparison of central brain (cerebrospinal and extracellular fluids) and peripheral blood kinetics of phenytoin after intravenous phenytoin and fosphenytoin [17].
• Adverse events associated with fosphenytoin generally were related to the central nervous system and were similar to those associated with phenytoin, except for a higher incidence of transient pruritus with fosphenytoin [18].

Associations of C07840 with other chemical compounds

• Fosphenytoin is metabolized (conversion half-life of 8 to 15 min) to phenytoin by endogenous phosphatases [2].
• They include calcium channel antagonists, NMDA receptor antagonists, lubeluzole, CDP-choline, the free radical scavenger tirilizad, anti-intercellular adhesion molecule-1 (ICAM-1) antibody, GM-1 ganglioside, clomethiazole, the sodium channel antagonist fosphenytoin, and piracetam [19].

Gene context of C07840

• With fosphenytoin treatment 5 min after ischemia, hippocampal CA1 pyramidal neurons remained at near control level (13.90 +/- 0.92), however, GFAP staining was not significantly changed [20].

Analytical, diagnostic and therapeutic context of C07840

• Fosphenytoin cross-reacted with both immunoassays, but to a greater extent with TDx [21].
• Intramuscular fosphenytoin is a safe and well-tolerated alternative to oral phenytoin when oral administration is not feasible [22].
• Although fosphenytoin can cross-react with phenytoin immunoassays, no fosphenytoin was detected by a sensitive HPLC method in any sample that was tested for its presence [4].
• Cardiac arrest after fast intravenous infusion of phenytoin mistaken for fosphenytoin [23].
• CONCLUSIONS: Fosphenytoin sodium, either undiluted in polypropylene syringes or diluted with NaCl 0.9% or D5W in PVC bags, remains stable for at least 30 days at room temperature, under refrigeration, or frozen [24].

References