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Factors that influence the pharmacokinetics of lamotrigine in Japanese patients with epilepsy

  • Pharmacokinetics and Disposition
  • Published:
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Abstract

Purpose

Lamotrigine (LTG) is used to treat epilepsy. The variability of LTG pharmacokinetics among individuals may be attributed to polymorphisms in the genes of uridine diphosphate glucuronosyltransferases (UGTs) 1A4 and UGT2B7 and/or combination with other drugs. In this study, we evaluated the association between LTG concentrations and patient characteristics such as genetic polymorphisms and the co-administration of antiepileptic drugs.

Methods

We recruited 122 patients with epilepsy. LTG concentrations were measured in blood samples from each patient under steady-state condition. We assessed the influence of multiple factors on LTG concentrations and derived a formula for predicting LTG concentrations using multiple linear regression analysis.

Results

We derived a formula to predict LTG concentrations that considers the daily dose of LTG, body weight, valproic acid concentration, phenytoin co-administration, and the co-administration of phenobarbital and/or carbamazepine as well as UGT1A4 142T>G and UGT2B7 -161C>T polymorphisms (adjusted coefficients of determination R 2 = 0.734). Furthermore, we used this formula to reveal a strong positive correlation between measured and predicted LTG concentrations (r 2 = 0.76, p < 0.001).

Conclusion

We derived a formula that will be useful in clinical practice for predicting LTG concentrations in patients with epilepsy.

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Authors and Affiliations

  1. Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan

    Kazuyuki Inoue, Eri Suzuki, Toshiki Takahashi, Akiko Umemura, Keita Hirai, Daiki Tsuji & Kunihiko Itoh

  2. Department of Clinical Research, National Epilepsy Center, NHO Shizuoka Institute of Epilepsy and Neurological Disorders, 886 Urushiyama, Aoi-ku, Shizuoka City, Shizuoka, 420-8688, Japan

    Yoshiaki Yamamoto, Yukitoshi Takahashi, Katsumi Imai & Yushi Inoue

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  1. Kazuyuki Inoue
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  2. Yoshiaki Yamamoto
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Correspondence to Kunihiko Itoh.

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Inoue, K., Yamamoto, Y., Suzuki, E. et al. Factors that influence the pharmacokinetics of lamotrigine in Japanese patients with epilepsy. Eur J Clin Pharmacol 72, 555–562 (2016). https://doi.org/10.1007/s00228-016-2008-2

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  • DOI: https://doi.org/10.1007/s00228-016-2008-2

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