The safety tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients

Bradley Boucher, Claudio A. Feler, J. Christine Dean, David D. Michie, Benjamin K. Tipton, Kenneth R. Smith, Ronald E. Kramer, Byron Young, Bruce R. Parks, Alan R. Kugler

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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%) than in the phenytoin group (25%, p<0.05). Reductions in infusion rates were required in 17% and 36% of fosphenytoin and phenytoin recipients, respectively. No significant difference was observed relative to adverse events or seizure frequency between the groups. Trough plasma phenytoin concentrations were approximately 10 μg/ml or greater in patients receiving at least 3 days of intramuscular and intravenous fosphenytoin. Trough phenytoin concentrations were similar between patients receiving intravenous phenytoin and fosphenytoin on all study days. Conclusion. Fosphenytoin can be administered intramuscularly and intravenously in neurosurgical patients to achieve and maintain therapeutic phenytoin concentrations for up to 14 days. Both routes are safe and well tolerated. Intravenous fosphenytoin is significantly better tolerated than intravenous phenytoin sodium in this patient subset.

Original languageEnglish (US)
Pages (from-to)638-645
Number of pages8
JournalPharmacotherapy
Volume16
Issue number4
StatePublished - Jul 1 1996

Fingerprint

Neurosurgery
Phenytoin
Intravenous Administration
Pharmacokinetics
Safety
fosphenytoin
Prodrugs
Double-Blind Method
Pharmaceutical Preparations
Anticonvulsants
Multicenter Studies

All Science Journal Classification (ASJC) codes

  • Pharmacology (medical)

Cite this

Boucher, B., Feler, C. A., Dean, J. C., Michie, D. D., Tipton, B. K., Smith, K. R., ... Kugler, A. R. (1996). The safety tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients. Pharmacotherapy, 16(4), 638-645.

The safety tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients. / Boucher, Bradley; Feler, Claudio A.; Dean, J. Christine; Michie, David D.; Tipton, Benjamin K.; Smith, Kenneth R.; Kramer, Ronald E.; Young, Byron; Parks, Bruce R.; Kugler, Alan R.

In: Pharmacotherapy, Vol. 16, No. 4, 01.07.1996, p. 638-645.

Research output: Contribution to journalArticle

Boucher, B, Feler, CA, Dean, JC, Michie, DD, Tipton, BK, Smith, KR, Kramer, RE, Young, B, Parks, BR & Kugler, AR 1996, 'The safety tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients', Pharmacotherapy, vol. 16, no. 4, pp. 638-645.
Boucher, Bradley ; Feler, Claudio A. ; Dean, J. Christine ; Michie, David D. ; Tipton, Benjamin K. ; Smith, Kenneth R. ; Kramer, Ronald E. ; Young, Byron ; Parks, Bruce R. ; Kugler, Alan R. / The safety tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients. In: Pharmacotherapy. 1996 ; Vol. 16, No. 4. pp. 638-645.
@article{f581fcda7d35434c8b96d212373d3ca2,
title = "The safety tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients",
abstract = "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{\%}) than in the phenytoin group (25{\%}, p<0.05). Reductions in infusion rates were required in 17{\%} and 36{\%} of fosphenytoin and phenytoin recipients, respectively. No significant difference was observed relative to adverse events or seizure frequency between the groups. Trough plasma phenytoin concentrations were approximately 10 μg/ml or greater in patients receiving at least 3 days of intramuscular and intravenous fosphenytoin. Trough phenytoin concentrations were similar between patients receiving intravenous phenytoin and fosphenytoin on all study days. Conclusion. Fosphenytoin can be administered intramuscularly and intravenously in neurosurgical patients to achieve and maintain therapeutic phenytoin concentrations for up to 14 days. Both routes are safe and well tolerated. Intravenous fosphenytoin is significantly better tolerated than intravenous phenytoin sodium in this patient subset.",
author = "Bradley Boucher and Feler, {Claudio A.} and Dean, {J. Christine} and Michie, {David D.} and Tipton, {Benjamin K.} and Smith, {Kenneth R.} and Kramer, {Ronald E.} and Byron Young and Parks, {Bruce R.} and Kugler, {Alan R.}",
year = "1996",
month = "7",
day = "1",
language = "English (US)",
volume = "16",
pages = "638--645",
journal = "Pharmacotherapy",
issn = "0277-0008",
publisher = "Pharmacotherapy Publications Inc.",
number = "4",

}

TY - JOUR

T1 - The safety tolerability, and pharmacokinetics of fosphenytoin after intramuscular and intravenous administration in neurosurgery patients

AU - Boucher, Bradley

AU - Feler, Claudio A.

AU - Dean, J. Christine

AU - Michie, David D.

AU - Tipton, Benjamin K.

AU - Smith, Kenneth R.

AU - Kramer, Ronald E.

AU - Young, Byron

AU - Parks, Bruce R.

AU - Kugler, Alan R.

PY - 1996/7/1

Y1 - 1996/7/1

N2 - 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%) than in the phenytoin group (25%, p<0.05). Reductions in infusion rates were required in 17% and 36% of fosphenytoin and phenytoin recipients, respectively. No significant difference was observed relative to adverse events or seizure frequency between the groups. Trough plasma phenytoin concentrations were approximately 10 μg/ml or greater in patients receiving at least 3 days of intramuscular and intravenous fosphenytoin. Trough phenytoin concentrations were similar between patients receiving intravenous phenytoin and fosphenytoin on all study days. Conclusion. Fosphenytoin can be administered intramuscularly and intravenously in neurosurgical patients to achieve and maintain therapeutic phenytoin concentrations for up to 14 days. Both routes are safe and well tolerated. Intravenous fosphenytoin is significantly better tolerated than intravenous phenytoin sodium in this patient subset.

AB - 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%) than in the phenytoin group (25%, p<0.05). Reductions in infusion rates were required in 17% and 36% of fosphenytoin and phenytoin recipients, respectively. No significant difference was observed relative to adverse events or seizure frequency between the groups. Trough plasma phenytoin concentrations were approximately 10 μg/ml or greater in patients receiving at least 3 days of intramuscular and intravenous fosphenytoin. Trough phenytoin concentrations were similar between patients receiving intravenous phenytoin and fosphenytoin on all study days. Conclusion. Fosphenytoin can be administered intramuscularly and intravenously in neurosurgical patients to achieve and maintain therapeutic phenytoin concentrations for up to 14 days. Both routes are safe and well tolerated. Intravenous fosphenytoin is significantly better tolerated than intravenous phenytoin sodium in this patient subset.

UR - http://www.scopus.com/inward/record.url?scp=9444232847&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9444232847&partnerID=8YFLogxK

M3 - Article

C2 - 8840370

AN - SCOPUS:9444232847

VL - 16

SP - 638

EP - 645

JO - Pharmacotherapy

JF - Pharmacotherapy

SN - 0277-0008

IS - 4

ER -