title: Phenytoin-loading: pharmacokinetic comparison between an intravenous bolus injection and a diluted standard solution.
abstract: Phenytoin (PHT) is considered a first or second choice in the treatment of status epilepticus that is refractory to benzodiazepines. The use of an intravenous bolus injection of PHT is hazardous due to the risk of cardiac conduction disturbances, dose-dependent side effects in general, as well as the possibility of severe necrotic lesions in case of extravasation. We compared the number and intensity of side effects and serum level profiles of a highly concentrated, non-dilutable bolus (46 mg/ml) of PHT [Fenytoin, DAK] with a dilutable standard solution (1.5 mg/ml) [Phenhydan] administered intravenously in 500 ml saline. Six healthy volunteers received both regiments (9.1 mg/kg). The diluted solution showed a curvilinear saturation curve with a lower concentration maximum (C-max) than the concentrated solution. Lower toxicity of the diluted solution was indicated by a clinical rating of side effects. Based on a higher incidence and degree of side effects following administration of the more concentrated formulation of PHT, compared with the more diluted preparation, we recommend the use of the less concentrated formulation.
authors.affiliation: University Clinic of Neurology, Hvidovre Hospital, Denmark.
authors.forename: B B
authors.initials: BB
authors.lastname: Andersen
authors.forename: A
authors.initials: A
authors.lastname: Møller
authors.forename: L
authors.initials: L
authors.lastname: Gram
authors.forename: N O
authors.initials: NO
authors.lastname: Jensen
authors.forename: M
authors.initials: M
authors.lastname: Dam
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity
chemical_list: D010672:Phenytoin