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

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.

Safety of an intravenous formulation of lamotrigine.

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-ß-cyclodextrin and stable-labeled can be given safely as a tracer replacement dose.

Long-term use of felbamate: clinical outcomes and effect of age and concomitant antiepileptic drug use on its clearance.

PURPOSE: To determine the effects of long-term use of felbamate (FBM) on weight, complete blood count, liver function tests, and seizure control, and also to determine the effect of age on FBM clearance. METHODS: A computerized prospective database was used to identify all subjects who had FBM listed as one of their antiepileptic drugs (AEDs) during their most recent clinic visit. Medical records from each patient were then reviewed for inclusion criteria [treatment >2 years, FBM initiated at the study clinic, data for pre-FBM (Time-1; T1), one-year exposure to FBM (Time-2; T2), and the latest visit (Time-3; T3)]. Clinical information was abstracted from clinic charts. RESULTS: Seventy-seven patients (F = 41, M = 36; ages 10-69 years) met entry criteria. Mean treatment time was 7.4 years, with the longest 20.3 years. Significant weight loss (mean 5.1 kg; p < 0.001) occurred from T1 to T2, but weight was regained by T3. No clinically significant changes in laboratory parameters occurred. Older age was associated with a significant decrease in FBM clearance (p = 0.01). Significant reduction in generalized tonic-clonic seizures was seen at both T2 (p < 0.001) and T3 (p < 0.001) compared with seizure frequency at T1. DISCUSSION: Our results suggest that long-term FBM use is associated with persistent decrease of seizures and no clinically significant changes in major laboratory parameters. Older age correlated with reduced apparent clearance of FBM. The patient population described in this study were long-term users of FBM who were continuing to use the drug, and thus this study does not constitute an "intent to treat" study.

Safety of an IV formulation of carbamazepine.

An intravenous formulation of carbamazepine (CBZ) was administered to 113 (60 male; 53 female) persons with epilepsy aged 19-87 years. Subjects received 100mg of study drug as replacement for 100mg of their usual morning dose of CBZ. There were no significant changes in blood pressure or heart rate suggesting that this formulation can be developed as replacement therapy for persons unable to take oral CBZ.

The validity of epilepsy or seizure documentation in nursing homes.

Recent studies have reported that epilepsy and seizures are common in nursing homes. Prevalence has been reported to range from 5 to 9% and antiepileptic drug (AED) use is even more common. Most of these studies have relied on various forms of nursing home records, but the validity of this source data, while assumed, has not been verified. This study evaluated the degree of agreement between the Minimum Data Set (MDS), both paper and electronic versions, and actual medical records available at the nursing home. Records of 144 residents were evaluated; agreement between paper and electronic versions of the MDS was 97.8%. Agreement between the paper version of the MDS and neurologists review of the nursing home record was 92.3%. However, the criteria for diagnosing epilepsy or seizure were not well documented. Nevertheless, the agreement among nursing home records, paper MDS and electronic MDS is great enough to allow the electronic MDS to be used as a research tool, but more investigation of the actual criteria used by nursing home physicians in diagnosing epilepsy and seizures is necessary.