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39 results on '"Patsalos, P.N."'

5. Brand-to-generic levetiracetam switch in patients with epilepsy in a routine clinical setting

Author

Markoula, S. Chatzistefanidis, D. Gatzonis, S. Siatouni, A. Siarava, E. Verentzioti, A. Kyritsis, A.P. Patsalos, P.N.

Abstract

Purpose The therapeutic equivalence of generic and brand antiepileptic drugs, based on studies performed on healthy volunteers, has been questioned. We compare, in a routine clinical setting, brand versus generic levetiracetam (LEV) bioequivalence in patients with epilepsy and also the clinical efficacy and tolerability of the substitution. Methods A prospective, open-label, non-randomized, steady-state, multiple-dose, bioequivalence study was conducted in 12 patients with epilepsy (5 females), with a mean age of 38.4 ± 16.2 years. Patients treated with the brand LEV (Keppra; UCB Pharma) were closely followed for a four-week period and subsequently switched to a generic LEV (Pharmaten) and followed for another four-week period. Blood samples were collected at the end of each 4-week period, during a dose interval for each formulation, for LEV concentration measurements by liquid chromatography mass spectrometry. Steady-state area under the curve (AUC) and peak plasma concentration (Cmax) data were subjected to conventional average bioequivalence analysis. Secondary clinical outcomes, including seizure frequency and adverse events, were recorded. Results Patients had epilepsy for a mean period of 14.1 ± 10.6 years and the mean daily LEV dose was 2583.3 ± 763.7 mg. The mean AUC ± SD and Cmax ± SD was 288.4 ± 86.3 (mg/L) h and 37.8 ± 10.4 mg/L respectively for brand LEV and 319.2 ± 104.7 (mg/L) h and 41.6 ± 12.3 mg/L respectively for the generic LEV. Statistic analysis showed no statistical significant difference in bioequivalence. Also, no change in seizures frequency and/or adverse events was recorded. Conclusions In our clinical setting, generic LEV was determined to be bioequivalent to brand LEV. Furthermore, seizures frequency or/and adverse events were not affected upon switching from brand to generic LEV. © 2017 British Epilepsy Association

Published
2017

7. The anti epileptic vigabatrin induces in the EEG of rats behaviour-independent increase of delta - and decrease of beta power

Author

Karakurum, E., Bouwman, B.M., Patsalos, P.N., Jongsma, M.L.A., Broek, P.L.C. van den, Coenen, A.M.L., and Rijn, C.M. van

Subjects
genetic structures, Cognitive neuroscience
Abstract

Item does not contain fulltext Vigabatrin and diazepam both are GABAergic drugs. Vigabatrin enhances the concentration of endogenous GABA by inhibiting GABA-transaminase, while diazepam enhances the efficacy of the endogenous GABA present. As may be expected, the clinical effects of the two drugs overlap: e.g. both have anti-epileptic effects and both decrease the level of vigilance. The similarity of the effects on the EEG is however less clear. During slow-wave sleep, in drug-free rats, the EEG consists of high-voltage delta waves. Despite the induction of sleep, diazepam enhances the power of the high frequency beta band. This phenomenon is called pharmacological dissociation. In contrast, vigabatrin has been shown to slow down the EEG; the power in the delta and theta bands increases while that of the beta band decreases. However in those studies behavioural changes were not taken into consideration. The aim of the present study was to investigate, in the rat, the effect of vigabatrin on behaviour and on behaviour-related EEG.

Published
2001

9. The importance of drug interactions in epilepsy therapy

Author

Patsalos, P.N., Fröscher, W., Pisani, F., Rijn, C.M. van, Patsalos, P.N., Fröscher, W., Pisani, F., and Rijn, C.M. van

Abstract

Item does not contain fulltext, Long-term anti-epileptic drug (AED) therapy is the reality for the majority of patients diagnosed with epilepsy. One AED will usually be sufficient to effectively control seizures, but a significant proportion of patients will need to receive a multiple AED regimen. Furthermore, polytherapy may be necessary for the treatment of concomitant disease. Also, the fact that over-the-counter drugs and nutritional supplements are increasingly being self-administered by patients needs to be considered. Therefore, the probability of patients with epilepsy experiencing drug interactions is high, particularly with the traditional AEDs, which are highly prone to drug interactions. Physicians prescribing AEDs to patients with epilepsy must, therefore, be aware of the potential for drug interactions and the effects (pharmacokinetic and pharmacodynamic) that can occur both during combination therapy and upon drug withdrawal. Whilst pharmacokinetic interactions are numerous and well described, pharmacodynamic interactions are few and usually concluded by default. Perhaps the most clinically significant pharmacodynamic interaction is that of lamotrigine and valproic acid; these drugs exhibit synergistic efficacy when co-administered in patients with refractory partial and generalised seizures. Hepatic metabolism is often the target for pharmacokinetic drug interactions and enzyme-inducing drugs such as phenytoin, phenobarbitone and carbamazepine will readily enhance the metabolism of other AEDs (e.g. lamotrigine, topiramate and tiagabine). The enzyme-inducing AEDs also enhance the metabolism of many other drugs (e.g. oral contraceptives, antidepressants and warfarin) so that therapeutic efficacy of co-administered drugs is lost unless the dosage is increased. Valproate inhibits the metabolism of phenobarbitone and lamotrigine, resulting in an elevation in the plasma levels of the inhibited drugs and consequently an increased risk of toxicity. The inhibition of the metabolism of carba

Published
2003

10. Selection of Antiepileptic Drug Polytherapy Based on Mechanisms of Action: The Evidence Reviewed

Author

Deckers, C.L.P., Czuczwar, S.J., Hekster, Y.A., Keyser, A.J.M., Kubova, H., Meinardi, H., Patsalos, P.N., Renier, W.O., Rijn, C.M. van, Deckers, C.L.P., Czuczwar, S.J., Hekster, Y.A., Keyser, A.J.M., Kubova, H., Meinardi, H., Patsalos, P.N., Renier, W.O., and Rijn, C.M. van

Abstract

Item does not contain fulltext, Purpose: When monotherapy with antiepileptic drugs (AEDs) fails, combination therapy is tried so as to improve effectiveness, by improving either efficacy, or tolerability, or both. We have reviewed the available studies (both animal and human) on AED polytherapy to determine whether AEDs can be selected for combination therapy based on their mechanisms of action, and if so, which combinations are associated with increased effectiveness. Because various designs and methods of analysis have been used in these studies it was also necessary to evaluate the appropriateness of these approaches. Methods: Published papers reporting on AED polytherapy in animals or humans were identified by Medline search and by checking references cited in these papers. Results: 39 papers were identified reporting on two-drug AED combinations. Several combinations were reported to offer improved effectiveness, but no uniform approach was used in either animal or human studies for the evaluation of pharmacodynamic drug interactions; efficacy was often the only endpoint. Conclusions: There is some evidence that AED polytherapy based on mechanisms of action may enhance effectiveness. In particular, combining a sodium channel blocker with a drug enhancing GABAergic inhibition appears to be advantageous. Combining two GABA mimetic drugs or combining an AMPA antagonist with a NMDA antagonist may enhance efficacy, but tolerability is sometimes reduced. Combining two sodium channel blockers seems less promising. However, given the incomplete knowledge of the pathophysiology of seizures and indeed of the exact mechanisms of action of AEDs, an empirical but rational approach for evaluating AED combinations is of fundamental importance. This would involve appropriate testing of all possible combinations in animal models and for advantageous combinations to be subsequently evaluated in clinical trials. Testing procedures in animals should include the isobologram method and the concept of drug load sho

Published
2000

13. Visual field constriction

Author

Sills, G. J., primary, Patsalos, P.N., additional, Butler, E., additional, Forrest, G., additional, Ratnaraj, N., additional, and Brodie, M.J., additional

Published
2001
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30. A comparison of the efficacy of carbamazepine and the novel anti-epileptic drug levetiracetam in the tetanus toxin model of focal complex partial epilepsy.

Author

Doheny, H.C., Whittington, M.A., Jefferys, J.G.R., and Patsalos, P.N.

Subjects
TETANUS toxin, CARBAMAZEPINE, ANTICONVULSANTS, EPILEPSY, HIPPOCAMPUS (Brain), DRUG dosage
Abstract

1 The tetanus toxin seizure model which is associated with spontaneous and intermittent generalized and non-generalized seizures, is considered to reflect human complex partial epilepsy. The purpose of the present study was to investigate and compare the anticonvulsant effects of carbamazepine with that of levetiracetam, a new anti-epileptic drug in this model. 2 One μl of tetanus toxin solution (containing12mLD[sub 50]μl[sup-1] of tetanus toxin) was placed stereotactically into the rat left hippocampus resulting in generalized and non-generalized seizures. Carbamazepine(4 mg kg[sup-1] h[sup-1])and levetiracetum (8 and 16 mg kg[sup-1] h[sup-1]) were administered during a 7 day period via an osmotic minipump which was placed in the peritoneal cavity. 3 Carbamazepine (4 mg kg[sup-1] h[sup-1]) exhibited no significant anticonvulsant effect, compared to control, when the entire 7 day study period was evaluated but the reduction in generalized seizures was greater (35.5%) than that for non-generalized seizures (12.6%), However, during the first 2 days of carbamazepine administration a significant reduction in both generalized seizure frequency (90%) and duration (25%) was observed. Non-generalized seizures were unaffected. This time-dependent anticonvulsant effect exactly paralleled the central (CSF) and peripheral (serum) kinetics of carbamazepine in that steady-stat concentrations declined over time, with the highest concentrations achieved during the first 2 days. Also there was a significant 27.3% reduction in duration of generalized seizures during the 7 day study period (p = 0.000l). 4 Levetiracetam administration (8 and 16 mg kg[sup-1] h[sup-1]) was associated with a dose-dependent reduction in the frequency of both generalized (39 v 57%) and non-generalized (36 v 41%) seizures. However, seizure suppression was more substantial for generalized seizures. Also a significant dose-dependent reduction in overall generalized seizure duration was observed. 5 These data provide experimental evidence for the clinical efficacy of levetiracetam for the management of patients with complex partial seizures. Furthermore, levetiracetam probably does not act by preventing ictogenesis per se but acts to reduce seizure severity and seizure generalization. [ABSTRACT FROM AUTHOR]

Published
2002
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31. The new generation of GABA enhancers. Potential in the treatment of epilepsy.

Author

Czuczwar, S.J. and Patsalos, P.N.

Subjects
*TREATMENT of epilepsy, *AMINOBUTYRIC acid, *SPASM treatment, *ANTICONVULSANTS
Abstract

gamma-Aminobutyric acid (GABA) is considered to be the major inhibitory neurotransmitter in the brain and loss of GABA inhibition has been clearly implicated in epileptogenesis. GABA interacts with 3 types of receptor: GABAA, GABAB and GABAC. The GABAA receptor has provided an excellent target for the development of drugs with an anticonvulsant action. Some clinically useful anticonvulsants, such as the benzodiazepines and barbiturates and possibly valproic acid (sodium valproate), act at this receptor. In recent years 4 new anticonvulsants, namely vigabatrin, tiagabine, gabapentin and topiramate, with a mechanism of action considered to be primarily via an effect on GABA, have been licensed. Vigabatrin elevates brain GABA levels by inhibiting the enzyme GABA transaminase which is responsible for intracellular GABA catabolism. In contrast, tiagabine elevates synaptic GABA levels by inhibiting the GABA uptake transporter, GAT1, and preventing the uptake of GABA into neurons and glia. Gabapentin, a cyclic analogue of GABA, acts by enhancing GABA synthesis and also by decreasing neuronal calcium influx via a specific subunit of voltage-dependent calcium channels. Topiramate acts, in part, via an action on a novel site of the GABAA receptor. Although these drugs are useful in some patients, overall, they have proven to be disappointing as they have had little impact on the prognosis of patients with intractable epilepsy. Despite this, additional GABA enhancing anticonvulsants are presently under development. Ganaxolone, retigabine and pregabalin may prove to have a more advantageous therapeutic profile than the presently licensed GABA enhancing drugs. This anticipation is based on 2 characteristics. First, they act by hitherto unique mechanisms of action in enhancing GABA-induced neuronal inhibition. Secondly, they act on additional antiepileptogenic mechanisms. Finally, CGP 36742, a GABAB receptor antagonist, may prove to be particularly useful in the management of primary generalised absence seizures. The exact impact of these new GABA-enhancing drugs in the treatment of epilepsy will have to await their licensing and a period of postmarketing surveillance. As to clarification of their role in the management of epilepsy, this will have to await further clinical trials, particularly direct comparative trials with other anticonvulsants. [ABSTRACT FROM AUTHOR]

Published
2001
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32. Satellite Symposia.

Author

Scheltens, P., Waldemar, G., Lilienfeld, S., De Deyn, P., Oertel, W.H., Gerstner, A., Brooks, D.J., Grosset, D.G., Dam, M., Schmidt, B., Patsalos, P.N., and French, J.A.

Subjects
NEUROLOGY, ALZHEIMER'S disease, DEMENTIA
Abstract

Presents several abstracts on neurology. 'Developments in Imaging: Progression of Alzheimer's Disease'; 'Diagnosing other Dementias'; 'Long-term Stabilization of the Patient with Alzheimer's Disease.'

Published
2000

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