Kazuyuki Inoue1, Yoshiaki Yamamoto2, Eri Suzuki1, Toshiki Takahashi1, Akiko Umemura1, Yukitoshi Takahashi2, Katsumi Imai2, Yushi Inoue2, Keita Hirai1, Daiki Tsuji1, Kunihiko Itoh3. 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. 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. 3. Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan. itohk@u-shizuoka-ken.ac.jp.
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.
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.
Authors: Sharmila Das; Dong Guo; Xiaohui Jiang; Wenlei Jiang; Yan Shu; Tricia Y Ting; James E Polli Journal: Pharm Res Date: 2020-02-26 Impact factor: 4.200