Steady-state pharmacokinetics and bioavailability of immediate-release and extended-release formulations of lamotrigine in elderly epilepsy patients: Use of stable isotope methodology

J Clin Pharmacol. 2015 Oct;55(10):1101-8. doi: 10.1002/jcph.522. Epub 2015 Aug 18.


A classic 2-period crossover bioavailability study was conducted to evaluate the relative and absolute bioavailability of immediate-release (IR) and extended-release (XR) lamotrigine formulations under steady-state conditions in elderly patients with epilepsy. On treatment days, each subject's morning dose (IR or XR lamotrigine) was replaced with an intravenous 50-mg dose of stable-labeled lamotrigine. Lamotrigine concentrations were measured at 13 points between 0 and 96 hours. XR and IR lamotrigine formulations were similar with respect to steady-state area under the concentration-time curve from 0 to 24 hours (AUC0-24 h ss), average concentration (Cavg, ss), and trough concentration (Cτ, ss). A 33% lower fluctuation in concentrations with XR was observed relative to IR lamotrigine. The time to peak concentration (Tmax, ss) was delayed for XR lamotrigine (3.0 vs 1.3 hours) with lower peak concentration (15% lower). The absolute bioavailability for IR and XR formulations was 73% and 92%, respectively. The formulations were bioequivalent with respect to AUC0-24 h ss, Cτ, ss, and Cavg, ss indicating that it may be possible to switch directly from IR to XR lamotrigine without changes in the total daily dose.

Keywords: elderly; extended-release; immediate-release; lamotrigine; stable isotope.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravenous
  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / blood
  • Anticonvulsants / pharmacokinetics*
  • Biological Availability
  • Carbon Isotopes
  • Cross-Over Studies
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / pharmacokinetics
  • Epilepsy / drug therapy
  • Epilepsy / metabolism*
  • Female
  • Humans
  • Lamotrigine
  • Male
  • Middle Aged
  • Nitrogen Isotopes
  • Triazines / administration & dosage
  • Triazines / blood
  • Triazines / pharmacokinetics*


  • Anticonvulsants
  • Carbon Isotopes
  • Delayed-Action Preparations
  • Nitrogen Isotopes
  • Triazines
  • Lamotrigine