Frequencies of UGT1A4*2 (P24T) and *3 (L48V) and their effects on serum concentrations of lamotrigine
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- 作者：Arne Reimers ; Wenche Sjursen ; Grethe Helde…
- 关键词：UGT1A4 ; Polymorphisms ; Lamotrigine ; Glucuronidation ; Serum concentration
- 刊名：European Journal of Drug Metabolism and Pharmacokinetics
- 出版年：2016
- 出版时间：April 2016
- 年：2016
- 卷：41
- 期：2
- 页码：149-155
- 全文大小：445 KB
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Wenche Sjursen (2) (3)
Grethe Helde (4)
Eylert Brodtkorb (4) (5)
1. Department of Clinical Pharmacology, St. Olavs University Hospital, Trondheim, Norway
2. Department of Laboratory Medicine, Children’s and Women’s Health, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
3. Department of Pathology and Medical Genetics, St. Olavs University Hospital, Trondheim, Norway
4. Department of Neuroscience, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
5. Department of Neurology and Clinical Neurophysiology, St. Olavs University Hospital, Trondheim, Norway - 刊物主题：Pharmacology/Toxicology; Pharmacy; Human Physiology; Pharmaceutical Sciences/Technology; Medical Biochemistry;
- 出版者：Springer Paris
- ISSN：2107-0180
文摘
The gene encoding uridine diphosphate glucuronosyltransferase (UGT) 1A4 shows considerable polymorphism. Several common drugs are metabolised by UGT1A4, among them lamotrigine (LTG). Experimental and clinical studies suggest that certain variants of UGT1A4 are associated with altered enzyme activity. However, results are conflicting. This clinical study aimed to investigate the frequencies of two common UGT1A4 variants, *2 (P24T) and *3 (L48V), and their potential effects on serum concentrations of LTG. The *2 variant was associated with a trend towards higher serum concentrations, while the *3 variant was associated with significantly lower serum concentrations of LTG. The calculated allele frequencies were in the same range as in earlier studies on Caucasian populations. To our knowledge, this is the first study suggesting a clinical effect of UGT1A4*2. Further study is needed to confirm this finding.