title: Influence of the UGT2B7 -161C>T polymorphism on the population pharmacokinetics of lamotrigine in Thai patients.
abstract: OBJECTIVE
  A high inter-individual variability in the pharmacokinetics of lamotrigine has been observed. Lamotrigine is primarily metabolized by UGT1A4 and UGT2B7, both of which show genetic polymorphisms. Both genetic and non-genetic factors may influence the pharmacokinetics of lamotrigine. The aim of this study was to determine the pharmacokinetic parameters of lamotrigine and to investigate the effect of genetic variants of UGT1A4 and UGT2B7 and various non-genetic factors on its pharmacokinetics.
  
  
  METHODS
  Four single nucleotide polymorphisms (SNPs; UGT1A4 142 T>G, UGT1A4 70C>T, UGT2B7 372A>G, UGT2B7 -161C>T) were identified using the TaqMan Allelic Discrimination Assay. Data were analyzed using NONMEM. Model evaluation was performed using the bootstrap approach and predictive check.
  
  
  RESULTS
  A total of 116 samples were obtained from 75 patients and included in the population analysis. The use of enzyme inducers, valproic acid, and the UGT2B7-161 C>T SNP were found to significantly influence lamotrigine apparent clearance (CL/F). Lamotrigine CL/F in patients carrying the UGT2B7 -161 CT or TT SNP was 18% lower than that in patients carrying the UGT2B7 -161 CC SNP.
  
  
  CONCLUSIONS
  Both genetic and non-genetic factors were found to influence lamotrigine pharmacokinetics. These factors should be considered when determining lamotrigine dosing. The model presented here could be useful for lamotrigine dose adjustment in clinical practice.
authors.affiliation: Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Noppaket
authors.initials: N
authors.lastname: Singkham
authors.forename: Somchai
authors.initials: S
authors.lastname: Towanabut
authors.forename: Surang
authors.initials: S
authors.lastname: Lertkachatarn
authors.forename: Baralee
authors.initials: B
authors.lastname: Punyawudho
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics*; D044466:Asian People / Q000235:genetics*; D001711:Biotransformation; D016009:Chi-Square Distribution; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D017711:Nonlinear Dynamics; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013785:Thailand; D014227:Triazines / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014227:Triazines; C019787:bilirubin glucuronoside glucuronosyltransferase; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase; D000077213:Lamotrigine