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Clinical trial with an experimental taurine derivative, taltrimide, in epileptic patients
Abstract:
The antiepileptic effect, effects on EEG, and tolerability of taltrimide, a new taurine derivative, were studied in this open clinical trial in 27 patients with severe epilepsy resistant to conventional drugs. After the 2-week control phase, taltrimide was given in gradually increasing doses up to 4.0 g/day--this dose used for 12 days. Taltrimide was given over 4 weeks and it was gradually withdrawn over 2 weeks. The frequency of seizures increased statistically significantly during the trial with increasing dose of taltrimide and decreased again in the withdrawal phase of the trial. Of six dropouts, one had status epilepticus, and in two patients increased number or severity of seizures necessitated withdrawal of taltrimide. There were no changes in EEG recordings or in laboratory data for safety evaluation. Taltrimide penetrated well through the blood-brain barrier, with the concentration of its main metabolite, phthalimidoethanesulphonamide, in cerebrospinal fluid, about half that in serum. The concentration of phenytoin increased statistically significantly, and there was a significant decrease in serum carbamazepine concentration during the taltrimide treatment. The anticonvulsive effect of taltrimide observed in animal experiments could not be confirmed in this study; in contrast, the seizures increased statistically significantly during taltrimide treatment. The reason for this remains obscure. The doses used, the significant drug interactions, or the patient material seemingly do not explain totally the noticed increase in seizure frequency. One explanation may be that taltrimide has proconvulsive properties in humans.
Insights
Taltrimide, a new taurine derivative, unexpectedly increased seizure frequency in patients with severe epilepsy, contrary to animal study findings. Further research is needed to understand its proconvulsive properties in humans.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Taltrimide is a novel taurine derivative investigated for epilepsy treatment.
- Severe epilepsy resistant to conventional drugs presents a significant clinical challenge.
Purpose of the Study:
- To evaluate the antiepileptic effect, EEG changes, and tolerability of taltrimide.
- To assess taltrimide's efficacy in patients with drug-resistant epilepsy.
Main Methods:
- An open clinical trial involving 27 patients with severe epilepsy.
- Gradual dose escalation of taltrimide up to 4.0 g/day over 4 weeks, followed by a 2-week withdrawal period.
- Monitoring of seizure frequency, EEG recordings, laboratory safety data, and drug interactions.
Main Results:
- Seizure frequency significantly increased during taltrimide treatment and decreased during withdrawal.
- No significant changes were observed in EEG or laboratory safety data.
- Taltrimide penetrated the blood-brain barrier; its main metabolite was found in cerebrospinal fluid.
- Significant interactions were noted: increased phenytoin and decreased carbamazepine serum concentrations.
Conclusions:
- The study did not confirm the anticonvulsive effect of taltrimide seen in animal models; instead, it showed a proconvulsive effect in humans.
- The exact reason for the increased seizure frequency remains unclear but may involve proconvulsive properties of taltrimide.
- Further investigation is warranted to elucidate taltrimide's mechanism of action and clinical utility in epilepsy.