Pharmacokinetics of Lamotrigine in Children in the Absence of other Antiepileptic Drugs

Chao, Chen; Casale, Eugene J.; Duncan, Benjamin; Culverhouse, Elizabeth H.; Gilman, Jamie T.

doi:10.1592/phco.19.6.437.31052

Cited by 45 publications

(28 citation statements)

References 26 publications

(23 reference statements)

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“…[70] Plasma binding is unaffected by therapeutic concentrations of phenytoin, phenobarbital and valproic acid (valproate sodium). [64] The apparent volume of distribution in 12 children with epilepsy receiving single doses of lamotrigine (2 mg/kg) in the absence of other antiepileptic agents was 1.5 L/kg, [57] which is comparable with values obtained in healthy Table I. Summary of the pharmacokinetic properties of lamotrigine in children a…”

Section: Absorption and Distributionsupporting

confidence: 62%

“…[66] After a single oral dose of 2 mg/kg, a mean maximum plasma concentration (C max ) of 1.48 mg/L (range 0.7 to 2.09 mg/L) was attained after a mean of 4.1 hours in 12 children aged between 6 months and 12 years receiving lamotrigine in the absence of other agents. [57] The time to reach maximum plasma concentrations (t max ) shows wider interindividual variability in children (typically 1 to 6 hours) [57,59] compared with adults (1 to 3 hours). [55] Lamotrigine pharmacokinetics are linear: C max and area under the plasma concentration-time curve (AUC) values are directly proportional to lamotrigine dose in the 30 to 450mg range in both children [61] and adults with epilepsy.…”

Section: Absorption and Distributionmentioning

confidence: 99%

“…[66] None of the metabolites are thought to be pharmacologically active. [25,77] In comparative studies of lamotrigine monotherapy, plasma clearance and volume of distribution values were higher in children (0.038 L/h/kg and 1.5 L/kg) [57] than adults (0.021 to 0.035 L/h/kg and 0.9 to 1.3 L/kg [78] ); elimination half-lives were broadly similar in children and in adults (32.3 hours in children [57] versus 23 to 37 hours in adults [78] ). Plasma clearance in children aged under 5 years is 2 to 3 times higher than that of adults.…”

Section: Metabolism and Eliminationmentioning

confidence: 99%

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Lamotrigine

Culy¹,

Goa²

2000

Paediatric Drugs

214

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Although published clinical evidence is still limited in paediatric populations, lamotrigine is an effective and generally well tolerated broad-spectrum agent for adjunctive treatment of refractory seizures in children, most notably in those with Lennox-Gastaut syndrome. Results of direct comparisons with other antiepileptic agents are needed to determine more clearly the place of lamotrigine, particularly relative to newer agents, in the treatment of childhood epilepsy. The potential for serious rash in recipients of lamotrigine should also be kept in mind. Nonetheless, lamotrigine is a welcome addition to the available treatments for refractory childhood epilepsy, particularly Lennox-Gastaut syndrome.

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Section: Absorption and Distributionsupporting

confidence: 62%

Section: Absorption and Distributionmentioning

confidence: 99%

Section: Metabolism and Eliminationmentioning

confidence: 99%

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Lamotrigine

Culy¹,

Goa²

2000

Paediatric Drugs

214

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“…All pediatric patients were trained for the behavioral tests and underwent at least one practice session in a mock-scanner after training. In order to increase the likelihood of capturing absence seizures during the EEG-fMRI scans, patients stopped taking medication for up to 48 hours prior to scanning (Barceloux, 1998; Buchanan and Kinkel, 1969; Chen et al, 1999; Hvidberg, 1976). Though some activating procedures, such as hyperventilation, sleep deprivation, or photic stimulation, may increase the chances of absence seizures, they were not used in this study.…”

Section: Methodsmentioning

confidence: 99%

Dynamic Time Course of Typical Childhood Absence Seizures: EEG, Behavior, and Functional Magnetic Resonance Imaging

et al. 2010

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Absence seizures are 5-10 s episodes of impaired consciousness accompanied by 3-4 Hz generalized spike-and-wave discharge on electroencephalography (EEG). The time course of functional magnetic resonance imaging (fMRI) changes in absence seizures in relation to EEG and behavior is not known. We acquired simultaneous EEG-fMRI in 88 typical childhood absence seizures from nine pediatric patients. We investigated behavior concurrently using a continuous performance task or simpler repetitive tapping task. EEG timefrequency analysis revealed abrupt onset and end of 3-4 Hz spike-wave discharges with a mean duration of 6.6 s. Behavioral analysis also showed rapid onset and end of deficits associated with electrographic seizure start and end. In contrast, we observed small early fMRI increases in the orbital/medial frontal and medial/lateral parietal cortex Ͼ5 s before seizure onset, followed by profound fMRI decreases continuing Ͼ20 s after seizure end. This time course differed markedly from the hemodynamic response function (HRF) model used in conventional fMRI analysis, consisting of large increases beginning after electrical event onset, followed by small fMRI decreases. Other regions, such as the lateral frontal cortex, showed more balanced fMRI increases followed by approximately equal decreases. The thalamus showed delayed increases after seizure onset followed by small decreases, most closely resembling the HRF model. These findings reveal a complex and long-lasting sequence of fMRI changes in absence seizures, which are not detectable by conventional HRF modeling in many regions. These results may be important mechanistically for seizure initiation and termination and may also contribute to changes in EEG and behavior.

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“…Evaluating the hours. Chen et al [93] studied a single 2 mg/kg dose in 12 children subset of children aged 2-12 years, 158 were randomized to (aged 3.8-11.3 years) with seizures. They reported an oral CL of lamotrigine and 75 patients received carbamazepine.…”

Section: Comparative Trialsmentioning

confidence: 99%

Use of Second-Generation Antiepileptic Drugs in the Pediatric Population

Chung

Eiland

2008

Pediatric Drugs

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Epilepsy is common in the pediatric population. Nine second-generation antiepileptic drugs have been approved in the US for use in epilepsy over the past 15 years: felbamate, gabapentin, lamotrigine, topiramate, tiagabine, levetiracetam, oxcarbazepine, zonisamide, and pregabalin. Their use in pediatric patients is fairly widespread, despite most of these agents not having US FDA indications for use. Felbamate and gabapentin were the first two second-generation antiepileptic drugs to be approved in the US. Felbamate use has been limited because of the occurrence of hepatotoxicity and aplastic anemia. Although gabapentin is a fairly well tolerated antiepileptic drug, its use has also been limited as a result of inconsistent efficacy and concern about seizure exacerbation. Lamotrigine and topiramate are broad-spectrum antiepileptic drugs with efficacy in a wide variety of seizure types. Both agents have some tolerability concerns: rash with lamotrigine and neuropsychiatric events with topiramate. There are very little data on tiagabine use in children, but this agent appears to be effective and to have a good tolerability profile. Levetiracetam is a second-generation antiepileptic agent that is available intravenously. Considering its good efficacy, fast onset of action, and low incidence of serious adverse effects, its use in the acute setting could potentially increase. Oxcarbazepine and zonisamide have been relatively well studied in pediatric seizure patients, including use as monotherapy. Both agents have demonstrated good efficacy and tolerability for patients as young as 1 month old. Vigabatrin and rufinamide are currently not available in the US, but have been shown to have some success in other countries. Pregabalin is the newest antiepileptic agent, but lacks pediatric data currently.

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Pharmacokinetics of Lamotrigine in Children in the Absence of other Antiepileptic Drugs

Cited by 45 publications

References 26 publications

Lamotrigine

Lamotrigine

Dynamic Time Course of Typical Childhood Absence Seizures: EEG, Behavior, and Functional Magnetic Resonance Imaging

Use of Second-Generation Antiepileptic Drugs in the Pediatric Population

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