Acute Effects of Lamotrigine (BW430C) in Persons With Epilepsy

Binnie, C. D.; Boas, W. van Emde; Kasteleijn‐Nolste‐Trenite, D. G. A.; Korte, Rainhart; Meijer, J. W. A.; Meinardi, H.; Miller, A A; Overweg, J.; Peck, A. W.; Wieringen, Astrid Van; Yuen, W. C.

doi:10.1111/j.1528-1157.1986.tb03536.x

Cited by 186 publications

(87 citation statements)

References 11 publications

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“…Part of this variability may be accounted for by fluctuations in VPA c'oncentrations among patients taking the same dose (26). Significant increases in phenobarbital (PB) serum concentrations (22,27) and lamotrigine elimination half-life, both attributable to changes in hepatic metabolism, also have been documented with Concomitant administration of VPA (28).…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Steady‐State Pharmacokinetics of Topiramate and Valproate in Patients with Epilepsy During Monotherapy and Concomitant Therapy

Rosenfeld

Liao²,

Kramer³

et al. 1997

Epilepsia

112

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Summary:Purpose: The steady-state pharmacokinetics of valproate (VPA) and topiramate (TPM) were compared during VPA monotherapy, concomitant VPA and TPM therapy, and TPM monotherapy to evaluate pharmacokinetic interactions.Methods: After a 3-week baseline period, 12 patients receiving VPA monotherapy (500 to 2,250 mg every 12 h) received TPM at three escalating doses (from 100 to 200 to 400 mg every 12 h), each for 2 weeks. Thereafter, the VPA dose was tapered by 25% weekly. Blood and urine samples were collected over 12-h intervals during VPA monotherapy and at the end of each stage of TPM dose escalation and TPM monotherapy.Results: All patients reached TPM monotherapy, and nine achieved satisfactory seizure control for 2 2 weeks without VPA. TPM plasma peak concentration (Cmax) and area under the concentration-versus-time curve during a 12-h dosing interval (AUC,,,) were slightly higher (17%; n = 8) during TPM monotherapy than during concomitant VPA therapy.

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Section: Discussionmentioning

confidence: 99%

Comparison of the Steady‐State Pharmacokinetics of Topiramate and Valproate in Patients with Epilepsy During Monotherapy and Concomitant Therapy

Rosenfeld

Liao²,

Kramer³

et al. 1997

Epilepsia

112

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“…progabide [1], lamotrigine [2], taltrimide, a taurine derivative [9], vigabatrine and loreclezole [11]. The experimental drug Org 6370 [8], however, has demonstrated paradoxical enhancement of photosensitivity with provocation of myoclonic seizures.…”

Section: Introductionmentioning

confidence: 99%

Photosensitive epilepsy: a model to study the effects of antiepileptic drugs. Evaluation of the piracetam analogue, levetiracetam

Trenité

Marescaux

Stodieck³

et al. 1996

Epilepsy Research

162

101

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General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. AbstractThe experimental antiepileptic drug, levetiracetam (UCB L059), a piracetam analogue has been investigated in photosensitive patients in the "photosensitivity model", an early phase II study. A total of 12 patients (10 females, 2 males) with a mean age of 21.5 years (range 13-38) were investigated during a 3 day period in 3 centres (France, The Netherlands, Germany), using the same standardised method. The subjects were either treated with a single oral dose of 250 mg, 500 mg, 750 mg or 1000 mg. In addition, 4 patients took 250 mg b.i.d, for 3-5 days, after which they were re-examined. In 9 of 12 photosensitive patients (75%) a clear suppression (3 patients) or abolishment (6 patients) of IPS evoked photoparoxysmal EEG responses was found. This effect appeared to be dose-dependent, the higher the dose the greater the effect; complete abolishment was only seen at dosages of 750 mg and 1000 mg, occurring at peak plasma levels and lasting between 6 and 30 h. There was no indication of pharmacokinetic interaction with concomitant antiepileptic drugs such as valproic acid, ethosuximide or phenobarbitone. No serious side-effects were seen and some patients reported enhancement of their mood. Two patients with myoclonic jerks noticed a clear reduction of their myoclonus, although this was not one of the objectives of the study. In conclusion, levetiracetam showed a clear antiepileptic effect in the photosensitivity model.

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“…This finding shows that absence of a PPR effect of a drug tested in only 1 dose should not be interpreted as evidence that the drug has no effect at all. CBZ is clearly a highly efficacious drug in patients with focal epilepsy, yet was either ineffective or poorly effective in this model at the standard dosage of 400 mg. A previous study by Binnie et al [4] reported that of 4 patients (3 with generalized seizures; 1 with partial onset seizures) treated with CBZ 400 mg doses (given as a liquid for rapid absorption), 2 had PPR abolishment. The study did not report serum levels [5] and it is unclear whether other factors, such as effects of concomitant AEDs, influenced CBZ responses.…”

Section: Discussionmentioning

confidence: 99%

“…If patients with a relatively stable IPS response are used as patients, studies can be performed using a study design that requires only 5-6 patients per dose tested. This protocol has been used to identify the antiepileptic effect of a number of AEDs (some now approved, some still in development), most notably levetiracetam (LEV), lamotrigine (LTG), brivaracetam, carisbamate, JZP4, YKP3089, and valproate (VPA) [1][2][3][4][5][6]. Drugs also have been tested that are sedatives, but not anticonvulsants, and these have failed to suppress photosensitivity [7], indicating that the assessment of PPR is both sensitive and specific.…”

Section: Introductionmentioning

confidence: 99%

Effects of Marketed Antiepileptic Drugs and Placebo in the Human Photosensitivity Screening Protocol

et al. 2014

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A study of epilepsy patients with a reproducible range of photoparoxysmal responses (PPR) (epileptiform discharges evoked by flashing lights) has been used as a "proofof-concept" trial to determine if novel potential antiepileptic drugs (AEDs) should proceed in development. The standard design for this trial requires a 3-day inpatient stay and is single-blind. We evaluated two marketed and effective AEDs-one narrow-spectrum [carbamazepine (CBZ)], and one broad-spectrum [levetiracetam (LEV)]-using a novel double-blinded, cross-over outpatient version of the trial to detect acute drug effects of the two marketed AEDs on photosensitivity. We tested 6 patients with a known stable photosensitivity response, using single oral doses of CBZ 400 mg and LEV 1000 mg, compared to 2 test days with single placebo doses. Patients who received LEV had the lowest mean PPR (compared with placebo and CBZ). The mixed effect model showed a significant effect of LEV in all eye closure conditions (p <0.001). There was no evidence of a significant change in PPR after CBZ or placebo treatment. In conclusion, LEV 1000 mg, but not CBZ 400 mg, was effective in suppressing photosensitivity within a 6-h period compared with placebo showing the ability of our novel photosensitivity trial design to demonstrate effects of broadspectrum AEDs. We cannot confirm the ability of the photosensitivity trial to detect the narrow-spectrum AED CBZ in our design. The novel outpatient study design is feasible and is expected to reduce costs compared with previous methodology.

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Acute Effects of Lamotrigine (BW430C) in Persons With Epilepsy

Cited by 186 publications

References 11 publications

Comparison of the Steady‐State Pharmacokinetics of Topiramate and Valproate in Patients with Epilepsy During Monotherapy and Concomitant Therapy

Comparison of the Steady‐State Pharmacokinetics of Topiramate and Valproate in Patients with Epilepsy During Monotherapy and Concomitant Therapy

Photosensitive epilepsy: a model to study the effects of antiepileptic drugs. Evaluation of the piracetam analogue, levetiracetam

Effects of Marketed Antiepileptic Drugs and Placebo in the Human Photosensitivity Screening Protocol

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