Smoking reduces serum levels of lamotrigine

Reinsberger, Claus; Dorn, Thomas; Krämer, Günter

doi:10.1016/j.seizure.2008.05.009

Cited by 26 publications

(16 citation statements)

References 10 publications

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“…We confirmed previously a demonstrated effect of smoking on LTG metabolism . Compared with non‐smokers, LTG clearance was 34% (95% CI 14.7, 59.0%) higher in patients who smoked.…”

Section: Discussionsupporting

confidence: 90%

“…Previous published studies showed that various factors such as weight , age , pregnancy , smoking , blood urea nitrogen : serum creatinine ratio , race , LTG daily dose [31], oral contraceptives and use of concurrent AEDs influence LTG plasma concentrations. Additionally, genetic polymorphisms in genes encoding drug‐metabolizing enzymes UGT1A4 , UGT2B7 and ABCB1 transporter [21] were also suggested to contribute to the IIV of LTG CL.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics of lamotrigine and its metabolite N‐2‐glucuronide: Influence of polymorphism of UDP‐glucuronosyltransferases and drug transporters

Milosheska

Lorber

Vovk

et al. 2016

Brit J Clinical Pharma

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AIMSThis study aimed to develop a population pharmacokinetic model for quantitative evaluation of the influence of genetic variants in metabolic enzymes and transporters on lamotrigine pharmacokinetics while taking into account the influence of various clinical, biochemical and demographic factors. METHODSWe included 100 patients with epilepsy on stable dosing with lamotrigine as mono or adjunctive therapy. Lamotrigine and lamotrigine N-2-glucuronide concentrations were determined in up to two plasma samples per patient. Patients were genotyped for UGT1A4, UGT2B7, ABCB1 and SLC22A1. Population pharmacokinetic analysis was performed by non-linear mixed effects modelling. Prior knowledge from previous pharmacokinetic studies was incorporated to stabilize the modelling process. A parent-metabolite model was developed to get a more detailed view on the covariate effects on lamotrigine metabolism. RESULTSWith a base model absorption rate (interindividual variability) was estimated at 1.96 h À1 (72.8%), oral clearance at 2.32 l h À1 (41.4%) and distribution volume at 77.6 l (30.2%). Lamotrigine clearance was associated with genetic factors, patient's weight, renal function, smoking and co-treatment with enzyme inducing or inhibiting drugs. In patients with UGT2B7-161TT genotype clearance was lower compared with GT and GG genotypes. Clearance was particularly high in patients with UGT2B7 372 GG genotype (compared with AA genotype it was 117%; 95% CI 44.8, 247% higher). CONCLUSIONSVariability in lamotrigine pharmacokinetics is large and quantification of its sources may lead to more precise individual treatment. Genotyping for UGT2B7 may be useful in various clinical settings. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Interindividual variability in lamotrigine pharmacokinetics is large and therapeutic drug monitoring may be warranted.• Lamotrigine disposition is mediated by UDP-glucuronosyltransferases, mainly by UGT1A4 and UGT2B7. ABCB1 and SLC22A1 transporters appear to be also involved.• Polymorphisms in UGT1A4, UGT2B7, ABCB1 and SLC22A1 genes affect protein activity and expression. WHAT THIS STUDY ADDS• Influences of polymorphisms of UGT2B7, patient's weight, renal function, smoking and co-treatment with enzyme inducing or inhibiting drugs on lamotrigine pharmacokinetics were quantified.• No significant association of lamotrigine pharmacokinetics with UGT1A4, SLC22A1 and ABCB1 polymorphisms was observed.• Clearance of lamotrigine-N-2-glucuronide depends on renal function and body weight.

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“…We confirmed previously a demonstrated effect of smoking on LTG metabolism . Compared with non‐smokers, LTG clearance was 34% (95% CI 14.7, 59.0%) higher in patients who smoked.…”

Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of lamotrigine and its metabolite N‐2‐glucuronide: Influence of polymorphism of UDP‐glucuronosyltransferases and drug transporters

Milosheska

Lorber

Vovk

et al. 2016

Brit J Clinical Pharma

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“…21 We also evaluated the effect of smoking on LTG. Only 2 of 21 women were smokers, 1 in group B and 1 in group C. Individually, the mean clearance of LTG in smokers was relatively high, which could provide some support to the notion that smoking reduces the serum levels of LTG.…”

Section: Resultsmentioning

confidence: 99%

Lamotrigine kinetics within the menstrual cycle, after menopause, and with oral contraceptives

Wegner¹,

Edelbroek²,

Bulk³

et al. 2009

Neurology

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“…In this context, lamotrigine (LTG) is an AED widely prescribed in association both with first and/or second generation AEDs, which favors the possible occurrence of drug interactions, since its metabolism is known to be influenced by different AEDs (Reinsberger, Dorn, Krämer, 2008;Johannessen, Landmark, 2010). Regardless of the LTG linear pharmacokinetics, its plasma concentration values show high inter-individual variability, as commonly seen in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

“…Regardless of the LTG linear pharmacokinetics, its plasma concentration values show high inter-individual variability, as commonly seen in clinical practice. In addition to factors related to pharmacotherapy, there are other clinical, physiological, pathological and even demographic factors influencing the pharmacokinetic of LTG (Reinsberger, Dorn, Krämer, 2008;Patsalos et al, 2008).…”

Section: Introductionmentioning

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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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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Smoking reduces serum levels of lamotrigine

Cited by 26 publications

References 10 publications

Pharmacokinetics of lamotrigine and its metabolite N‐2‐glucuronide: Influence of polymorphism of UDP‐glucuronosyltransferases and drug transporters

Pharmacokinetics of lamotrigine and its metabolite N‐2‐glucuronide: Influence of polymorphism of UDP‐glucuronosyltransferases and drug transporters

Lamotrigine kinetics within the menstrual cycle, after menopause, and with oral contraceptives

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

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