Behavioural Neurology - Volume 3, issue Supplement 1

Authors: Dreifuss, F.E.

Article Type: Other

DOI: 10.3233/BEN-1990-31S101

Citation: Behavioural Neurology, vol. 3, no. Supplement 1, pp. v-vi, 1990

Authors: Johannessen, Svein I.

Article Type: Research Article

Abstract: The serum concentration achieved and maintained following the administration of a fixed drug dosage is a direct consequence of the interactions of a wide variety of interrelated processes, including drug absorption, distribution, metabolism, and excretion, and the physiological status of the patient. These interrelationships are reviewed with specific reference to the major anti-epileptic drugs, phenobarbitone, phenytoin, sodium valproate, and carbamazepine, as well as a new first-line antiepileptic, oxcarbazepine. Both older drugs, such as phenobarbitone and phenytoin, and newer drugs, such as carbamazepine (CBZ) and sodium valproate, have been studied extensively over the past years giving valuable information for drug …treatment. An important feature of oxcarbazepine (OXC) , which was developed through minimal changes in the structure of CBZ in order to improve on the tolerability of CBZ without sacrificing efficacy, is that its metabolites do not include the 11-epoxide which has been implicated in the side-effects of CBZ. In man, OXC is metabolized to a monohydroxy derivative which has independent anti-epileptic properties. OXC seems to lack several disadavantageous pharmacokinetic properties common to other major anti-epileptic drugs. OXC does not influence its own metabolism after repeated administration, in contrast to the auto-induction displayed by CBZ. The metabolism of OXC is not influenced by anti-epileptic co-medication and does not influence the kinetics of other anti-epileptic drugs – or if it does, then to a lesser extent than CBZ. Show more

DOI: 10.3233/BEN-1990-31S102

Citation: Behavioural Neurology, vol. 3, no. Supplement 1, pp. 1-11, 1990

Authors: Gram, Lennart

Article Type: Research Article

Abstract: Several avenues are being explored in the development of new anti-epileptic drugs (AEDs). For a number of years efforts have been directed towards compounds which may augment neuronal inhibition, and these efforts have resulted in the development of several valuable drugs. More recently, increased attention has been focused on the role which excitatory transmitters may play in epileptogenesis, and various substances which decrease excitation are currently being investigated at the preclinical level. Since considerable potential still resides in several of the drugs already on the market, resources have been spent on trying to modify/improve the chemical formula of some …of these substances, and a number of new drugs has emerged as a result of this approach. The major accomplishments reviewed here in the development of new anti-epileptic drugs suggest that even more successful advances may be achieved in the near future. Show more

DOI: 10.3233/BEN-1990-31S103

Citation: Behavioural Neurology, vol. 3, no. Supplement 1, pp. 13-19, 1990

Authors: Faigle, Johann W. | Menge, Guenter P.

Article Type: Research Article

Abstract: Hepatic oxygenases of the cytochrome P-450 family play a major role in the clearance of various anti-epileptic drugs. These enzymes are susceptible both to induction and to inhibition. Phenytoin, carbamazepine (CBZ), primidone, and phenobarbitone, for instance, are potent enzyme inducers. Other drugs, such as chloramphenicol, propoxyphene, verapamil, and viloxazine, inhibit cytochrome P-450. Pharmacokinetic behaviour is thus often altered, especially in combined medication, so that the dosage has to be re-adjusted if an optimum therapeutic outcome is to be ensured. Oxcarbazepine (OXC) is a keto analogue of CBZ. In the human liver the keto group is readily reduced, and the …resulting monohydroxy metabolite is cleared by glucuronidation. The two enzymes mediating these reactions, i.e. aldo-keto reductase and UDP-glucuronyltransferase, do not depend on cytochrome P-450. The monohydroxy metabolite is the major active substance in plasma. Its elimination is not enhanced by OXC. Moreover, OXC seems to have little effect on cytochrome P-450. Aldo-keto reductases and glucuronyltransferases are in general less sensitive to induction and inhibition than are P-450 dependent enzymes. On the whole, OXC possesses very little potential for metabolic drug interactions, and thus differs favourably from other anti-epileptic drugs. Show more

DOI: 10.3233/BEN-1990-31S104

Citation: Behavioural Neurology, vol. 3, no. Supplement 1, pp. 21-30, 1990

Authors: Dam, Mogens

Article Type: Research Article

Abstract: Altogether 235 patients with newly diagnosed epilepsy were randomly allocated to treatment with either oxcarbazepine (OXC) or carbamazepine (CBZ) in a double-blind multicentre trial. After a titration phase of 4–8 weeks the optimum individual dose of trial medication was determined and treatment with this dose was continued for another 48 weeks. The results of the study indicate that there is no significant difference in seizure frequency between OXC and CBZ; no correlation was found between the therapeutic effect and EEG in either treatment group. OXC caused significantly (p = 0.04) fewer “severe” side-effects than CBZ. Global evaluation of tolerability …showed a trend towards better tolerability of OXC. There way no correlation between either efficacy or tolerability and serum trough levels of the investigational drugs. Clinically relevant abnormal laboratory test findings were observed in two patients, both on CBZ. In conclusion, OXC is a major anti-epileptic drug, which is as effective as CBZ in the treatment of partial seizures and generalized convulsions. With fewer side-effects than CBZ, it represents a valuable alternative particularly in patients who develop side-effects which prevent optimum seizure control. Show more

DOI: 10.3233/BEN-1990-31S105

Citation: Behavioural Neurology, vol. 3, no. Supplement 1, pp. 31-34, 1990

Authors: Jensen, Peder Klosterskov

Article Type: Research Article

Abstract: The anti-epileptic activity of oxcarbazepine (OXC) was compared with that of carbamazepine (CBZ) and the primary active metabolite of OXC, a monohydroxy derivative (MHD). Altogether 255 patients receiving either OXC or MHD (192 and 63 patients respectively) were included in the analysis of efficacy. Out of these 255 patients a total of 40 were children. The duration of treatment varied between 8 and 24weeks. The daily dose of OXC or MHD varied between 600 and 5400 mg (in children 600–2400 mg). Out of five studies two were double-blind controlled studies (including a total of 105 patients) whereas the remaining three …were open studies. The results of these studies indicate that, in adults with epilepsy, there is no statistically significant difference in overall seizure frequency between CBZ and OXC. In one double-blind study the number of generalized tonic-clonic seizures was significantly less frequent during treatment with OXC than with CBZ. No statistically significant difference with regard to side-effects was observed between OXC and CBZ. The results in children with epilepsy show a statistically significant difference in seizure frequency in favour of OXC, in comparison with CBZ. Overall, the polytherapy studies in adults and children support the effectiveness and safety of oxcarbazepine. Show more

DOI: 10.3233/BEN-1990-31S106

Citation: Behavioural Neurology, vol. 3, no. Supplement 1, pp. 35-39, 1990

Article Type: Other

DOI: 10.3233/BEN-1990-31S107

Citation: Behavioural Neurology, vol. 3, no. Supplement 1, pp. 41-44, 1990