Influence of concurrent antiepileptic medication on the pharmacokinetics of lamotrigine as add‐on therapy in epileptic children

Vauzelle-Kervroëdan, F; Rey, Elisabeth; Cieuta, Cécile; Pariente-Khayat, Ann; Pons, Gérard; d'Athis, P; Bidault, Roselyne; Dulac, Olivier; Olivé, G

doi:10.1046/j.1365-2125.1996.31610.x

Cited by 47 publications

(22 citation statements)

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“…The model validation dataset contained a total of 508 concentrations collected from 148 patients (Table 1) enrolled in four studies, two single‐dose pharmacokinetic studies [18, 19] and two efficacy/safety trials [13, 14] of placebo‐controlled parallel design with LTG or placebo added to the existing AED therapy which was maintained unchanged during the trials (Table 2). The patient characteristics are summarized in Table 1.…”

Section: Methodsmentioning

confidence: 99%

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Validation of a population pharmacokinetic model for adjunctive lamotrigine therapy in children

Chen

2000

Brit J Clinical Pharma

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Aims This analysis was performed to validate a previously developed population pharmacokinetic model for lamotrigine in order to establish a basis for dosage recommendations for children. Methods (a) The importance of the covariates in the ®nal model was con®rmed using the model validation dataset. Population and individual (Bayesian estimate) pharmacokinetic parameters were estimated using both the initial model, which included none of the covariates, and the ®nal model. Accuracy and precision of parameter estimation and of concentration prediction were compared between the two models. (b) The performance in predicting the validation concentrations by the ®nal model parameters obtained previously from the model development dataset was assessed. (c) The parameters of the ®nal model were re®ned using a dataset combining both the development and validation data. Results Prediction performance of the ®nal pharmacostatistical model was superior to that of the initial model. The results of the validation con®rmed that concomitant antiepileptic drugs that increased or reduced lamotrigine clearance in adults had similar effects in children. The validation also veri®ed the linear relationship between weight and clearance. The previously seen small sex effect on clearance was found statistically insigni®cant. Conclusions The current analysis con®rmed the previous ®ndings. To achieve the same concentrations, children receiving enzyme-inducing antiepileptic drugs without valproate require higher doses than those receiving valproate; and heavier children require higher doses.

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Section: Methodsmentioning

confidence: 99%

“…Although most cases of epilepsy are diagnosed during childhood and adolescence, information on the pharmacokinetics of LTG in children is limited [17–19]. Conventional pharmacokinetic studies require extensive blood sampling, and are therefore difficult to conduct in children.…”

Section: Introductionmentioning

confidence: 99%

Validation of a population pharmacokinetic model for adjunctive lamotrigine therapy in children

Chen

2000

Brit J Clinical Pharma

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“…[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%

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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“…Blankenhorn et al (22) found 18 k g LTG/ml serum in one female who swallowed 3,000 mg LTG with suicidal intentions -2 h after ingestion. Comedication with CBZ or PHT has an enzyme-inducing effect (16,23,24) and should reduce the maximal serum concentrations. On the other hand, patients l and 4 received 600 mg ranitidinelday as additional medication.…”

Section: F P Meyer Et Almentioning

confidence: 99%

Lamotrigine Concentrations in Human Serum, Brain Tissue, and Tumor Tissue

et al. 1999

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Summary:Purpose: Although lamotrigine (LTG) has been used for years as an antiepilepic drug (AED), there are no data on penetration into the brain with the exception of a single case report. It was our aim to determine the LTG content in the brain and the tumor tissue and to bring the same into relation to the serum concentration and protein binding in neurosurgically operated patients.Methods: Neurosurgical intervention was performed on 1 1 patients with brain tumors. Tumor tissue was removed, and LTG kinetics was carried out for 12 h. LTG was determined by means of (HPLC) and the protein binding by means of ultrafiltration.Results: At the time of the section of the tumor, the LTG concentrations in the serum were an average of 3.7 kg/ml (range, 1.1-9.8); in the brain, an average of 4.8 pg/g (range, 1.0-14.9); and in the tumor, an average of 4.4 pg/g (range, 2.0-8.3). Brain/serum and tumor/serum ratios of 2.8 and 1.9, respectively, result from these data. The protein binding was on average 68% (range, 46-96).Conclusions: LTG is a lipophile AED with a moderate protein binding that penetrates brain tissue well and can be proven even in the tumor tissue.

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Influence of concurrent antiepileptic medication on the pharmacokinetics of lamotrigine as add‐on therapy in epileptic children

Cited by 47 publications

References 10 publications

Validation of a population pharmacokinetic model for adjunctive lamotrigine therapy in children

Validation of a population pharmacokinetic model for adjunctive lamotrigine therapy in children

Lamotrigine

Lamotrigine Concentrations in Human Serum, Brain Tissue, and Tumor Tissue

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