The Safety, Tolerability, and Pharmacokinetics of Fosphenytoin after Intramuscular and Intravenous Administration in Neurosurgery Patients

作者：Bradley A. Boucher, Claudio A. Feler, Jesse C. Dean, David D. Michie, Benjamin K. Tipton, Kenneth R. Smith, Ronald E. Kramer, Byron A. Young, Bruce R. Parks, Alan R. Kugler · 发表于：Pharmacotherapy The Journal of Human Pharmacology and Drug Therapy · 年份：1996 · DOI：10.1002/j.1875-9114.1996.tb03646.x · 被引用次数：54 · 研究领域：Pharmacological Effects and Toxicity Studies、Epilepsy research and treatment、Anesthesia and Sedative Agents

STUDY OBJECTIVE: To evaluate the safety, tolerability, and pharmacokinetic profile of fosphenytoin, a water-soluble phenytoin prodrug, after intramuscular and intravenous administration. DESIGN: Open-label study of intramuscular administration, and double-blind, randomized study of intravenous administration. SETTING: Six and ten hospitals throughout the United States for the intramuscular and intravenous multicenter studies, respectively. PATIENTS: Neurosurgical patients who required anticonvulsant prophylaxis or treatment. INTERVENTIONS: In the intramuscular study, 118 patients received loading doses ranging from 480-1500 mg phenytoin equivalents (PE) and daily maintenance doses ranging from 130-1250 mg PE for 3-14 days. In the intravenous study, 88 patients received fosphenytoin and 28 received phenytoin sodium for 3-14 days. Mean +/- SD loading doses and maintenance doses of intravenous fosphenytoin and phenytoin were 1082 +/- 299 mg PE and 411 +/- 221 mg PE, and 1082 +/- 299 mg and 422 +/- 197 mg, respectively. Trough phenytoin concentrations were measured daily in all patients. MEASUREMENTS AND MAIN RESULTS: Intramuscular fosphenytoin was safe and well tolerated, with no irritation found for 99% of all injection site evaluations. Adverse events associated with the drug occurred in 9% of patients, commonly those typical of the parent drug. For intravenous treatment, the frequency of mild irritation at the infusion site was significantly lower in the fosphenytoin group (6...