Lamotrigine and valproate pharmacokinetics interactions in epileptic patients

Lalić, M.; Cvejić, Jelena; Popović, Jovan; Božić, Ksenija; Goločorbin-Kon, Svetlana; Al‐Salami, Hani; Mikov, Momir

doi:10.1007/bf03191157

Cited by 36 publications

(26 citation statements)

References 26 publications

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“…As observed, the mean LTG plasma concentration seen in the "inhibitor group" was approximately four-fold higher than in the "inducers group", even with both groups presenting similar LTG dosages (mg/kg/day). Similar results were also found by Bootsma et al (2008), Lalic et al (2009) and Yamamoto et al (2012). These results suggest that there are prescriptions that are not being individualized according to the co-medications.…”

Section: Discussionsupporting

confidence: 77%

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Influence of the clinical profile of patients with refractory epilepsy on lamotrigine plasma concentration

Baldoni

Freitas‐Lima

Alexandre

et al. 2018

Braz. J. Pharm. Sci.

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The purpose of this work was to evaluate the influence of the clinical profile on lamotrigine (LTG) plasma concentrations from patients with refractory epileptic seizures. In this cross-sectional study, therapeutic monitoring of LTG, and questionnaires with 75 patients with refractory epileptic seizures of a Hospital in Ribeirão Preto-SP-Brazil were performed. The multiple linear regression model was used to verify association between the LTG plasma concentrations and the independent variables. Covariance analysis was used to compare the mean LTG plasma concentration among the co-medication groups. The LTG plasma concentration was associated both with the LTG dosage (mg/kg/day) (p=0.0096) and with the use of first generation antiepileptic drugs (AED) (p<0.01), being carbamazepine (CBZ) and phenytoin (PHT), the AEDs showing the most prominent influence in reducing LTG plasma concentrations. Adverse events, adherence to the pharmacological treatment, and epileptic seizures frequency, did not show significant correlation with LTG plasma concentration values. The conclusion is that LTG plasma concentration is significantly influenced by the LTG dosage and by the concomitant use of a first generation AED.

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Section: Discussionsupporting

confidence: 77%

“…Moreover, polytherapy is, in epilepsy treatment, a very common and unavoidable situation, which makes therapeutic drug monitoring an essential tool to manage drug interactions (Lalic et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Influence of the clinical profile of patients with refractory epilepsy on lamotrigine plasma concentration

Baldoni

Freitas‐Lima

Alexandre

et al. 2018

Braz. J. Pharm. Sci.

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“…However, the majority of lamotrigine plasma concentrations (six of seven) in patients receiving formulation B were in the range of 3 to 14 μg/mL, which has previously been suggested as the therapeutic range. [26,27] No dose-dependent adverse effects appeared in the patients, and all patients were seizure free. No statistically significant differences were found between dose-normalized concentrations of these two formulations (figure 3b).…”

Section: Resultsmentioning

confidence: 95%

Comparison of Dissolution Profiles and Serum Concentrations of Two Lamotrigine Tablet Formulations

et al. 2011

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Objective: The aim of this study was to investigate the extent of variations in lamotrigine serum concentrations between two immediate-release tablet formulations. Data were compared with in vitro difference and similarity tests on dissolution profiles of the two formulations.Methods: Dissolution characteristics of formulations A (reference) and B (test) were evaluated at three points spanning the physiologic pH range (pH 1.2, pH 4.5, pH 6.8). A model-independent approach of difference (f1) and similarity (f2) tests were applied to dissolution data. A clinical study was performed with 16 patients who were divided into two groups — one group received formulation A (n=9) and the other received formulation B (n=7). Lamotrigine steady-state concentrations were determined by high-performance liquid chromatography on a reverse-phase column.Results: There were no statistically significant differences in lamotrigine serum concentrations between the two groups, although formulation B had slightly higher mean concentration values (formulation A: 3.97±4.1 μg/mL; formulation B: 5.78±2.7 μg/mL). Dissolution profiles of the two formulations were similar in the pH 1.2 dissolution medium; however, the dissolution profiles of formulation B were outside the dissolution limit (≥85% at 15 minutes) in the pH 4.5 and 6.8 dissolution media.Conclusions: No significant changes in the serum concentrations of lamotrigine were seen between the two investigated formulations. There is no evidence to suggest that the differences in dissolution profiles at pH 4.5 and pH 6.8 affect the therapeutic efficacy of the formulations. It is evident that the doses of test formulation given to the patients were higher as a consequence of common assumption that generic products have a lower absorption rate, which is proven unnecessary in this study. This investigation was a pilot study and thus further investigations with a larger sample size are necessary to determine if there is a connection between dissolution profiles and the therapeutic effect of investigated formulations.

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“…Valproic acid, a known inhibitor of several UGT‐isoenzymes, causes a 77% increase in quetiapine concentration [7], indicating that glucuronidation may be an important route for quetiapine elimination. Likewise, the metabolism of lamotrigine is inhibited by valproic acid, probably via inhibition of UGT1A3 and maybe also UGT1A4 [8].…”

Section: Discussionmentioning

confidence: 99%

Possible drug–drug interaction between quetiapine and lamotrigine – evidence from a Swedish TDM database

Andersson

Björkhem‐Bergman

Lindh

2011

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Preliminary evidence from a single study indicates that co-medication with lamotrigine may reduce the serum concentration of quetiapine. Since both drugs are commonly used in bipolar disorder such a drug-drug interaction could be of great importance, but the findings need to be confirmed. WHAT THIS STUDY ADDS• The association between lamotrigine dosing and lowered quetiapine concentrations was confirmed in a small independent patient sample. The magnitude of the reduction (58%) indicated that the proposed drug-drug interaction may be of clinical importance. AIMThe aim of the present study was to investigate a previously proposed interaction between quetiapine and lamotrigine resulting in reduced serum quetiapine concentrations. METHODSData on 402 patients subjected to analysis of quetiapine concentration in serum were extracted from a routine therapeutic drug monitoring database. Among these patients, those concomitantly treated with lamotrigine (n = 22) were identified and matched with 22 controls receiving quetiapine while unexposed to lamotrigine. The dose-corrected quetiapine concentrations (C : D ratios) in the two groups were compared in both paired and unpaired analyses. RESULTSPatients co-treated with lamotrigine had a lower mean C : D ratio (0.71, 95% CI 0.46, 0.97) compared with controls (1.64, 95% CI 1.00, 2.28). Dose-corrected quetiapine concentrations were 58% lower in patients co-medicated with lamotrigine.

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Lamotrigine and valproate pharmacokinetics interactions in epileptic patients

Cited by 36 publications

References 26 publications

Influence of the clinical profile of patients with refractory epilepsy on lamotrigine plasma concentration

Influence of the clinical profile of patients with refractory epilepsy on lamotrigine plasma concentration

Comparison of Dissolution Profiles and Serum Concentrations of Two Lamotrigine Tablet Formulations

Possible drug–drug interaction between quetiapine and lamotrigine – evidence from a Swedish TDM database

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