Antiepileptic drugs comparative studies

From the examination of structure-activity relationships, it has been concluded that a phenyl moiety at C-6 as well as a 4-hydroxypiperidine side-chain attached to C-3 of the pyridazine system is essential for anticonvulsant activity in this class of compounds [184], Compounds (54) and (55) have been found to have similar anticonvulsant profiles in animals (mice, rats and baboons) [165, and literature cited therein] and to represent potent broad-spectrum antiepileptic drugs. Their potency with regard to antagonizing seizures (induced by electro-shock or various chemicals) has been compared with standard anticonvulsants like carbamazepine and phenobarbitone [185, 186], A quantitative electroencephalographic analysis of (55) has been published [187]. From in vitro studies it has been concluded that the anticonvulsant activities of these compounds are not mediated by an enhancement of GABAergic transmission or by an interaction with benzodiazepine receptor sites [ 165,186,187], On the other hand, in vivo experiments showed that (54), at anticonvulsant doses, increases the affinity of flunitrazepam for its central receptor site [ 186], Investigations of (54) and (55) in a behavioural test predictive of antianxiety activity revealed a marked difference in the pharmacological profiles of these structurally closely related compounds the dichloro compound SR 41378 (55) has also been found to possess anxiolytic (anticonflict) properties [165],... 

A review of HPLC methods for antiepileptic drug analysis was published in 1987 by Juergens.18 Standard analytical separations were compared with narrow-bore separations, and a 70% reduction in the cost of solvents was possible, owing to a reduction in flow rate from 1 ml/min for the analytical column to 0.3 ml/min for the narrow-bore column. Gayden et al.19 developed an isocratic method, using narrow-bore columns, to quantify adenosine (Ado) release by dispersed rat renal outer medullary cells under conditions of normoxia and hypoxia. Standard HPLC with UV detection has been the predominant method for studying the metabolic pathways of adenosine and measuring the Ado breakdown products inosine (Ino) and hypoxanthine (Hyp). However, the conventional methods lack reliability... 

Huetos et al. f 124] publi.shed a comparative. study on TLC of different cortico-steroids the results are depicted in Table 10.15. Kulkami et al. [125] published the TLC of phentoine (diphenyl hydanthoine, which is an antiepileptic and anticonvulsant drug). The Rf value and sensitivity were compared to those of several benzodiazepines. The results are depicted in Table 10.16. 

The effects of stiripentol have been studied in 41 children with severe myoclonic epilepsy in infancy in a randomized, placebo-controlled, add-on trial (2). There were adverse effects in 21 patients taking stiripentol (drowsiness and loss of appetite) compared with five taking placebo, and the adverse effects disappeared when the doses of other antiepileptic drugs were reduced in 12 of the 21 cases. 

Very few examples of outcomes research in neurological pharmacy exist. However, one historical control study determined that the implementation of a pharmacokinetics consultation service in an epilepsy clinic decreased seizure frequency and number of adverse effects compared with the baseline frequency in the 4 months prior to offering the service.A second study conducted in the pediatric epilepsy population described the effect of establishment of a specialty pediatric epilepsy clinic with clinical pharmacy services. Compared with patients seen before the beginning of the clinic, patients seen in the specialty clinic had decreased numbers of antiepileptic drugs and decreased doses of these medications. Frequency of seizures was not examined in this report. 

A study in 6 healthy subjects taking ethosuximide 500 mg daily found that the mean plasma levels of ethosuximide were reduced by 17%, from 32 to 27 mg/mL by carbamazepine 200 mg daily for 18 days. One individual had a 35% reduction in ethosuximide levels. Another study, which compared 10 epileptic patients (taking enzyme-inducing antiepileptic drugs, including 4 taking carbamazepine) with 12 healthy controls found that the epileptic group had markedly shorter (about halved) ethosuximide half-lives. ... 

These effects probably occur because these antiepileptics are potent liver enzyme inducers, which may increase the metabolism of teniposide by the liver and thereby reduce its levels. The authors of these reports therefore conclude that an increased dosage of teniposide will be needed in the presence of these antiepileptics to achieve systemic exposure to the drug comparable to that achievable in their absence. It may be preferable to use alternative antiepileptics (that are not enzyme inducers) in patients requiring teniposide. More study is needed. 

In 2005, in a sponsor s report of a doubleblind study, there was a slightly higher risk of suicidality in the antiepileptic drug-treated patients compared with those taking placebo and there were also reports of suicidality related to the branded formulation of gaba-pentin [18 ]. 

Comparative studies Oxcarbazepine has been compared with traditional antiepileptic drugs in 35 patients with brain tumor-related epilepsy in a retrospective observational study [216 ]. Oxcarbazepine and traditional antiepileptic drugs had similar efficacy but different patterns of adverse effects. Significantly fewer of those who took oxcarbazepine dropped out and in relation to serious adverse effects, only three of those who took oxcarbazepine compared with 13 of those who took other drugs had to stop treatment. As regards the total incidence of adverse effects, four patients had adverse effects during oxcarbazepine treatment compared with 15 of those who took other drugs. 

Comparative studies Phenytoin and levetiracetam Phenytoin has been compared retrospectively with levetiracetam for prophylaxis of early and late postoperative seizures in 315 patients [182 ]. Adverse effects prompting a change in antiepileptic drug therapy in only one patient taking levetiracetam, who had visual hallucinations, but in 38 (18%) of those who took phenytoin. In patients who were followed for at least 1 year and developed epilepsy, levetiracetam had also a higher retention rate. 

Eurap Study Group. Utilization of antiepileptic drugs during pregnancy comparative patterns in 38 countries based on data from the EURAP registry. Epilepsia 2009 50(10) 2305-9. 

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