Postictal inhibition of the somatosensory cortex.

Transient suppression of the motor cortex and of the speech areas cause well-described postictal phenomena following seizures involving the respective cortical areas. Pain is a rare symptom in epileptic seizures. We present a patient with painful tonic seizures in the left leg. The amplitude of the cortical component of the somatosensory evoked potential following stimulation of the left tibial nerve was reduced immediately after the seizure. Our findings suggest that the excitability of the sensory cortex is transiently reduced following a seizure involving the somatosensory area.

Diurnal lamotrigine plasma level fluctuations: clinical significance and indication of shorter half-life with chronic administration.

For therapeutic monitoring of antiepileptic drugs (AEDs), morning trough levels (MTLs) are generally used. For specific questions like verification of breakthrough seizures or reported toxicity, however, other measures such as minimal and maximal concentrations (C(min), C(max)) can be important and may require daily profiles. For clinical reasons, 20 daily profiles of lamotrigine (LTG) plasma levels were determined in nine patients. The results revealed fluctuations exceeding those expected from its elimination half-life (t(1/2)) of 22h as reported in the literature. Patients on twice-daily regimens without pharmacokinetic interactions exhibited C(min)/C(max) ratios between 0.62 and 0.69. Fluctuations were smaller in those co-medicated with valproate, and reached a ratio of 0.55 in those co-medicated with phenobarbital. The C(max) was as much as 58% above the MTL. Therefore, verification of complaints indicating toxicity requires determination of drug levels when the symptoms are present. Our findings indicate that the t(1/2) of LTG with chronic treatment is shorter than generally assumed, and suggest that a slow-release formulation could be helpful in achieving full seizure control in patients with a narrow individual therapeutic index for LTG.

Comparative daily profiles with different preparations of lamotrigine: a pilot investigation.

Comparative pharmacokinetic data obtained with different preparations of lamotrigine (LTG) are reported for the first time. Nine outpatients reporting problems attributed to shifts in the preparation of LTG used were admitted to hospital. Patients were treated with proprietary LTG for at least 2 weeks prior to admission. Daily profiles (DPs) spanning 24 hours were obtained by blood sampling at 3- or 4-hour intervals on Day 3 after admission. A second DP was obtained under similar conditions after generic LTG therapy for at least 7 days. LTG concentrations were determined by HPLC, and DPs were generated to compare pharmacokinetic parameters. In five of nine patients, parameters deviated beyond +/-10%. Even with the narrower bioequivalence requirements for mandatory substitution in Denmark, there are some patients who experienced serious clinical consequences (relapse in a seizure-free patient, status epilepticus, epidural hematoma due to ataxia with falls) in association with a change in preparation, and significant corresponding alterations in plasma levels could be demonstrated by comparative pharmacokinetic testing.

Lamotrigine therapeutic thresholds.

PURPOSE: To evaluate therapeutic drug monitoring (TDM) of lamotrigine (LTG) with establishment of individual therapeutic thresholds (TT) in outpatients of a tertiary epilepsy centre on monotherapy. METHODS: In the outpatient clinic of the Danish Epilepsy Centre, Dianalund, all patients treated in 2004 with LTG monotherapy were identified. Patients who had not reported seizures or adverse reactions in the last 6 months were considered seizure free and well-medicated on LTG monotherapy, and were further evaluated. Plasma levels from routine LTG TDM obtained by reversed-phase high-pressure liquid chromatography (HPLC) during up-titration were used to calculate the TT for each patient as the mean of the highest subtherapeutic and the lowest therapeutic level. RESULTS: Eighty-two patients undergoing LTG monotherapy were reported seizure free as defined above. In 34 the TT could not be calculated because they became seizure free on the first chosen dose. TTs of the remaining 48 patients ranged from 4.0 to 42.0 micromol/l. There were no differences between children and adults, and between generalized and localization-related epilepsies. The therapeutic levels of patients with undefined TT tended to be lower. The level-dose ratio in both groups varied only moderately indicating absence of major exogenous influences. CONCLUSION: Even in patients of a tertiary referral centre only a minority had high TTs and needed therapeutic levels in a range where toxicity is increasingly observed. TDM appears useful in LTG treatment both for the establishment of individual reference ranges and for the identification of the individual level-to-dose ratio.