Postmortem investigation of lamotrigine concentrations

Lamotrigine is a relatively new anticonvulsant. Therapeutic plasma concentr ations generally range from 1 to 4 mg/L, although several studies have show n that good control of epilepsy has been achieved with concentrations reach ing 10 mg/L generally, with little toxicity. In overdose, however, the drug has been linked to ECG changes that may suggest a possible arrythmogenic e ffect and hence cardiac toxicity. Lamotrigine has also been shown to cause encephalopathy and thus neurotoxicity. There is no information concerning postmortem lamotrigine concentrations an d their interpretation. We describe lamotrigine concentrations in postmorte m specimens including blood, liver, bile, vitreous humour, and urine from e ight cases. A high performance liquid chromatography (HPLC) method is descr ibed with extraction procedures for the various tissues. Two possible groups were identified. The first being the "broader therapeut ic" group with blood concentrations ranging from 0.9 to 7.2 mg/L and corres ponding liver concentrations ranging from 16 to 36 mg/kg. The second being a "supratherapeutic" group with blood concentrations ranging from 20 to 39 mg/L and corresponding liver concentrations ranging from 53 to 350 mg/kg. A lthough none of the eight cases described were attributed to overdose by la motrigine alone, the cause of death for one of the three cases in the "supr atherapeutic" group was given as mixed drug toxicity. Cause of death for th e remaining two cases in this group was reported as epilepsy. However, both these cases showed elevated concentrations of lamotrigine and both were co -medicated with valproic acid. Such co-administration has been shown in the literature to lead to elevated lamotrigine concentrations and a reduction in lamotrigine dose has been recommended. With such data, we highlight the importance of monitoring lamotrigine concentrations in cases co-medicated, particularly with valproic acid.