Safety of an intravenous formulation of lamotrigine

Jeannine M Conway; Angela K Birnbaum; Ilo E Leppik; Page B Pennell; James R White; John O Rarick; Rory P Remmel

doi:10.1016/j.seizure.2014.01.019

Safety of an intravenous formulation of lamotrigine

Seizure. 2014 May;23(5):390-2. doi: 10.1016/j.seizure.2014.01.019. Epub 2014 Jan 31.

Authors

Jeannine M Conway¹, Angela K Birnbaum², Ilo E Leppik³, Page B Pennell⁴, James R White⁵, John O Rarick¹, Rory P Remmel⁶

Affiliations

¹ Experimental and Clinical Pharmacology, 308 Harvard Street SE, Minneapolis, MN 55455, United States.
² Experimental and Clinical Pharmacology, 308 Harvard Street SE, Minneapolis, MN 55455, United States. Electronic address: birnb002@umn.edu.
³ Experimental and Clinical Pharmacology, 308 Harvard Street SE, Minneapolis, MN 55455, United States; Department of Neurology, 420 Delaware St. SE, University of Minnesota, Minneapolis, MN 55455, United States; MINCEP Epilepsy Care, 5775 Wayzata Boulevard, Minneapolis, MN 55416, United States.
⁴ Department of Neurology and Division of Women's Health at Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA 02115, United States.
⁵ MINCEP Epilepsy Care, 5775 Wayzata Boulevard, Minneapolis, MN 55416, United States.
⁶ Department of Medicinal Chemistry, 308 Harvard Street SE, University of Minnesota, Minneapolis 55455, MN, United States.

Abstract

Purpose: Intravenous (IV) formulations are useful when treating patients where oral administration is not possible and to study certain pharmacokinetic parameters such as bioavailability. We developed a stable-labeled IV formulation of lamotrigine (LTG) for studying pharmacokinetics in epilepsy patients.

Methods: Stable-labeled IV LTG was given to 20 persons with epilepsy (6 men; 14 women) with a mean age of 34.8 years (SD 11.7). A 50mg dose of LTG (stable labeled) was given intravenously and replaced 50mg of the regular morning oral dose of LTG (unlabeled, commercially available formulation).

Results: No significant changes in blood pressure, heart rate, or adverse events including rash were attributed to administration of a 50-mg dose of the intravenous LTG formulation.

Conclusion: Our results show that LTG base that is complexed with 2-hydroxypropyl-β-cyclodextrin and stable-labeled can be given safely as a tracer replacement dose.

Keywords: Cyclodextrin; Epilepsy; Intravenous; Lamotrigine; Safety.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

2-Hydroxypropyl-beta-cyclodextrin
Administration, Oral
Adolescent
Adult
Aged
Aged, 80 and over
Anticonvulsants / administration & dosage
Anticonvulsants / adverse effects
Anticonvulsants / therapeutic use*
Drug Administration Schedule
Epilepsy / drug therapy*
Female
Humans
Lamotrigine
Male
Middle Aged
Triazines / administration & dosage
Triazines / adverse effects
Triazines / therapeutic use*
Young Adult
beta-Cyclodextrins / administration & dosage
beta-Cyclodextrins / adverse effects
beta-Cyclodextrins / therapeutic use

Substances

Anticonvulsants
Triazines
beta-Cyclodextrins
2-Hydroxypropyl-beta-cyclodextrin
Lamotrigine

Abstract

Publication types

MeSH terms

Substances

Grants and funding