Bioequivalence of Lamotrigine 50-mg Tablets in Healthy Male Volunteers: a Randomized, Single-Dose, 2-Period, 2-Sequence Crossover Study

Pérez-Lloret, Santiago; Olmos, Lisandro; Mena, Felicitas; Pieczanski, P.; Moncalvo, Juan José Rodríguez

doi:10.1055/s-0032-1321859

Cited by 5 publications

(3 citation statements)

References 12 publications

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“…However, all side effects of the medication (LOV and LTG) have been described after longer application whereas in the present study patients will receive LOV only four times and LTG only one time. In one patient receiving LTG, a mild rash following the administration reported has been reported [ 21 ]. In an own placebo-controlled, randomized, double-blind study using the same single dose of LTG (300 mg), no side effects, apart from mild sedation/dizziness and lacrimation have been reported in 26 young healthy adults [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

Improvement of synaptic plasticity and cognitive function in RASopathies—a monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (SynCoRAS)

Jung

Egert-Schwender

Schossow

et al. 2023

Trials

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Background Cognitive impairment is a common medical issue in rat sarcoma (RAS) pathway disorders, so-called RASopathies, like Neurofibromatosis type 1 (NF1) or Noonan syndrome (NS). It is presumed to be caused by impaired synaptic plasticity. In animal studies, pathway-specific pharmacological interventions with lovastatin (LOV) and lamotrigine (LTG) have been shown to improve synaptic plasticity as well as cognitive function. The aim of this clinical trial is to translate the findings of animal studies to humans and to probe the effect of lovastatin (NS) and lamotrigine (NS and NF1) on synaptic plasticity and cognitive function/alertness in RASopathies. Methods Within this phase IIa, monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (syn. SynCoRAS), three approaches (approaches I–III) will be carried out. In patients with NS, the effect of LTG (approach I) and of LOV (approach II) is investigated on synaptic plasticity and alertness. LTG is tested in patients with NF1 (approach III). Trial participants receive a single dose of 300 mg LTG or placebo (I and III) and 200 mg LOV or placebo (II) daily for 4 days with a cross-over after at least 7 days. Synaptic plasticity is investigated using a repetitive high-frequency transcranial magnetic stimulation (TMS) protocol called quadri-pulse theta burst stimulation (qTBS). Attention is examined by using the test of attentional performance (TAP). Twenty-eight patients are randomized in groups NS and NF1 with n = 24 intended to reach the primary endpoint (change in synaptic plasticity). Secondary endpoints are attention (TAP) and differences in short interval cortical inhibition (SICI) between placebo and trial medication (LTG and LOV). Discussion The study is targeting impairments in synaptic plasticity and cognitive impairment, one of the main health problems of patients with RASopathies. Recent first results with LOV in patients with NF1 have shown an improvement in synaptic plasticity and cognition. Within this clinical trial, it is investigated if these findings can be transferred to patients with NS. LTG is most likely a more effective and promising substance improving synaptic plasticity and, consecutively, cognitive function. It is expected that both substances are improving synaptic plasticity as well as alertness. Changes in alertness may be a precondition for improvement of cognition. Trial registration The clinical trial is registered in ClinicalTrials.gov (NCT03504501; https://www.clinicaltrials.gov; date of registration: 04/11/2018) and in EudraCT (number 2016–005022-10).

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Section: Discussionmentioning

confidence: 99%

Improvement of synaptic plasticity and cognitive function in RASopathies—a monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (SynCoRAS)

Jung

Egert-Schwender

Schossow

et al. 2023

Trials

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“…In healthy volunteers, using lower doses of lamotrigine (25mg/day) may be hard to measure in clinical laboratory method; while high doses cause serious adverse events [12]. Serum AST, ALT, urea, and creatinine were altered and the value of some of them were significant and others were not.…”

Section: Discussionmentioning

confidence: 99%

“…Healthy rats treated with lamotrigine for different periods noted a significant increase in blood parameters when compared with the control group [11]. There were no significant changes in hematological parameters among healthy males treated with 50mg lamotrigine [12] Milosheska et.al.…”

Section: Introductionmentioning

confidence: 99%

Hematological and Biochemical parameters study of female albino rats treated with lamotrigine drug

Shekha¹,

Maulood²

2019

Tikrit J. Pure Sci.

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The present study was aimed to investigate the possible effects of the anti-epileptic drug lamotrigine (LTG) on some haematological and biochemical parameters in adult female rats. Forty-eight female rats were divided into three groups (each group=16). Group one can be considered as a control group, group two and three administrated lamotrigine drugs orally at a dose of 3.57mg/kg body weight and 7.14mg/kg body weight for 7,14,21,28 day and all groups fed with standard rat feed. The results showed that there were significant (P≤0.05) changes in haematological parameters in group two and three when compared with the control group during all period except the mean level of corpuscular haemoglobin concentration (MCHC). The liver enzyme aspartate transaminase (AST) and alanine transaminase (ALT) and serum urea, creatinine with calcium, potassium, sodium and chloride ion showed significant alteration in the treated group, the relative organ weight showed significant changes in group two and three in comparison with control group during 7,14,21 and 28 days. Estradiol level in group three increased at 7, 14 and 21 day and decreased at 28 days of treatment when compared with group two and the control group. This study suggested that treatment of healthy female albino rats with therapeutic doses of lamotrigine drug for 28 days generally affect on included parameters in this study.

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A Physiologically Based Pharmacokinetic Model for Optimally Profiling Lamotrigine Disposition and Drug–Drug Interactions

Conner

Reed

Zhang

2018

Eur J Drug Metab Pharmacokinet

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Bioequivalence of Lamotrigine 50-mg Tablets in Healthy Male Volunteers: a Randomized, Single-Dose, 2-Period, 2-Sequence Crossover Study

Cited by 5 publications

References 12 publications

Improvement of synaptic plasticity and cognitive function in RASopathies—a monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (SynCoRAS)

Improvement of synaptic plasticity and cognitive function in RASopathies—a monocentre, randomized, double-blind, parallel-group, placebo-controlled, cross-over clinical trial (SynCoRAS)

Hematological and Biochemical parameters study of female albino rats treated with lamotrigine drug

A Physiologically Based Pharmacokinetic Model for Optimally Profiling Lamotrigine Disposition and Drug–Drug Interactions

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