title: Influence of uridine diphosphate glucuronosyltransferase inducers and inhibitors on the plasma lamotrigine concentration in pediatric patients with refractory epilepsy.
abstract: This study evaluated the influence of concomitant antiepileptic drugs (AEDs) on the plasma concentration of lamotrigine (LTG) in pediatric patients with epilepsy. We retrospectively reviewed 1653 plasma samples from 709 patients (aged 6 months to 16 years) and compared the concentration-to-dose ratio (CD ratio) of LTG among different AED regimens. The median CD ratio of patients receiving LTG monotherapy was 1.25 μg/mL/mg/kg. In patients receiving LTG plus VPA, the CD ratio was increased by about 140%. The CD ratio was elevated from a low VPA concentration (<40 μg/mL) and the increase was VPA concentration-dependent. In contrast, the median CD ratio of patients treated with LTG plus the inducers phenytoin, phenobarbital, and carbamazepine was 0.42, 0.63, and 0.66, respectively, and phenytoin significantly reduced the CD ratio in comparison with phenobarbital or carbamazepine (p < 0.001). Pediatric patients of all ages beyond infancy showed similar susceptibility to VPA or inducers, but infants had higher CD ratios compared with the other age groups. Among other AEDs, topiramate, ethosuximide, and rufinamide reduced the CD ratio. These findings should be useful for estimating interactions between LTG and concomitant AEDs.
authors.affiliation: Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Shizuoka, Japan; Department of Clinical Pharmaceutics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan. Electronic address: yamamoty-3@hosp.go.jp.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamamoto
authors.affiliation: Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Shizuoka, Japan; Department of Clinical Pharmaceutics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Shizuoka, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Imai
authors.affiliation: Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Shizuoka, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikeda
authors.affiliation: Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Shizuoka, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Shizuoka, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Nakai
authors.affiliation: Department of Clinical Research, National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Shizuoka, Japan.
authors.forename: Yushi
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Clinical Pharmaceutics, Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan; Laboratory of Clinical Pharmacokinetics and Drug Safety, Shizuoka General Hospital, Shizuoka, 420-8527, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kagawa
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004790:Enzyme Induction; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D014453:Glucuronosyltransferase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D006801:Humans; D007223:Infant; D000077213:Lamotrigine; D008297:Male; D012189:Retrospective Studies; D014227:Triazines / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D014227:Triazines; D014453:Glucuronosyltransferase; D000077213:Lamotrigine
keywords: Children; Drug interaction; Lamotrigine; Pharmacokinetics; Therapeutic drug monitoring