title: Factors that influence the pharmacokinetics of lamotrigine in Japanese patients with epilepsy.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  We derived a formula that will be useful in clinical practice for predicting LTG concentrations in patients with epilepsy.
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Inoue
authors.affiliation: 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.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Suzuki
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Umemura
authors.affiliation: 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.
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: 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.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imai
authors.affiliation: 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.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Hirai
authors.affiliation: Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka, 422-8526, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Tsuji
authors.affiliation: 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.
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Itoh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics; D006801:Humans; D007223:Infant; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014227:Triazines / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014227:Triazines; C019787:bilirubin glucuronoside glucuronosyltransferase; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; D000077213:Lamotrigine
keywords: Concentration; Epilepsy; Lamotrigine; Prediction formula; UGT1A4; UGT2B7