Distribution of Topiramate in a Medical Examiner's Case

Abstract

Topimarate (Topamax) is a novel antiepileptic drug. Its mode of action is multifactorial and involves blockage of voltage-dependent sodium channels. The drug was detected in a 15-year-old epileptic who died soon after switching seizure prescriptions. Topimarate was recovered by basic extraction with ethyl acetate and analyzed by gas chromatography-mass spectrometry using selected ion monitoring. Ions monitored were m/z 324 and m/z 110 for topiramate and m/z 98 for the internal standard mepivacane. The drug was quantitated in blood, vitreous humor, bile, stomach content, and liver: the concentrations were 8.9, 12.4, and 10.9 mg/L, 31 mg/total content, and 29 mg/kg, respectively. Topiramate was detected in urine but not quantitated. Other drugs identified in this case were 0.45 mg/L nordiazepam and 0.05 mg/L oxazepam in blood. No alcohol was detected in any of the specimens. The cause of death was seizure disorder with upper respiratory infection. The manner of death was determined as natural. To our knowledge, this is the first report of the presence of topiramate in postmortem specimens.

Interpreting Results of Ethanol, Carbamazepine and Topiramate in Putrefied Postmortem Specimens: A Case Report

“…Few case reports on topiramate levels in post-mortem specimens have been published until now. We have found much lower topiramate concentrations in both liver and kidney when compared with previous cases of intoxication described in literature [16,18,19]. In particular, liver concentrations of 29 µg/g [16] and 140 µg/g [19] were found in previous studies, which are higher than the value detected in this study (0,64 µg/g), as well as the kidney concentrations (55 µg/g vs 0,68 µg/g) [18].…”

“…Likewise, the levels of CBZ and CBZ-epox found in the kidney are lower than those detected in the acute intoxication cases [15]. Topiramate is well absorbed from the gastrointestinal tract, and peak plasma levels are usually obtained within 2-3 hours post-dose [16]. A small portion of drug is bound to plasma proteins.…”

“…The drug is primarily eliminated in the urine. Daily therapeutic dosage is 400-1000 mg/day [16] and the therapeutic plasma level is 2-25 µg/ml [17]. Few case reports on topiramate levels in post-mortem specimens have been published until now.…”

Therapeutic Drug Monitoring of the Newer Anti-Epilepsy Medications

“…The value of TDM of topiramate is mainly due to inter-individual variation in metabolism. Multiple analytical methodologies have been reported for the measurement of topiramate in plasma/serum including GC [166], GC/MS [167], HPLC [168], LC/MS [169,170], LC/MS/MS [171] and immunoassay [172,173]. …”

Topiramato: efectos secundarios a nivel ocular. Revisión a propósito de un caso

“…El fármaco da lugar a un aumento de los niveles de prostaglandinas que actúan desencadenando un edema de cuerpo ciliar a nivel local pero sin actuar a nivel sistémico 15 aunque se ha comprobado que atraviesa la barrera hematoencefálica y se ha detectado en vítreo 16 . La biomicroscopia ultrasónica muestra la presencia de un síndrome de efusión ciliocoroidea, edema y rotación anterolateral del cuerpo ciliar, con relajación zonular, cambios que conducen a un desplazamiento anterior del diafragma iris-cristalino y, como consecuencia se produce un estrechamiento de la cámara anterior responsable de la miopización y de la crisis de glaucoma agudo [17][18][19] .…”