UGT2B7_−161C>T Polymorphism Is Associated With Lamotrigine Concentration-to-Dose Ratio in a Multivariate Study

  title={UGT2B7\_−161C>T Polymorphism Is Associated With Lamotrigine Concentration-to-Dose Ratio in a Multivariate Study},
  author={Mar{\'i}a Blanca S{\'a}nchez and Jos{\'e} Luis Herranz and Carlos Leno and Rosa Arteaga and Agust{\'i}n Oterino and Elsa Mar{\'i}a Valdiz{\'a}n and Josep Mar{\'i}a Nicol{\'a}s and Javier Ad{\'i}n and Mehrdad Shushtarian and Juan A. Armijo},
  journal={Therapeutic Drug Monitoring},
Lamotrigine (LTG) is metabolized by UGT1A4 but UGT2B7 also contributes to its glucuronidation. The aim of this study was to determine whether UGT2B7_− 161C>T and UGT2B7_372A>G polymorphisms contribute to the intersubject variability in LTG concentration-to-dose ratio (LTG-CDR) in epileptic patients. Fifty-three white epileptic patients attending the Neuropediatric and Neurology Services at the Marqués de Valdecilla University Hospital, in whom LTG serum concentration was to be measured for… 

Influence of valproic acid concentration and polymorphism of UGT1A4*3, UGT2B7 -161C > T and UGT2B7*2 on serum concentration of lamotrigine in Chinese epileptic children

UGT1A4*3 polymorphism had an effect on LTG concentration only with VPA co-administration, and the effect was remarkable when VPA concentration was higher.

Factors that influence the pharmacokinetics of lamotrigine in Japanese patients with epilepsy

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 is derived.

UGT1A6- and UGT2B7-related valproic acid pharmacogenomics according to age groups and total drug concentration levels.

UGT1A6 and UGT2B7 genotypes were not related to significant changes in VPA metabolism, even after controlling for total drug concentration levels, and younger ages were associated with increased VPA clearance rate.

Population pharmacokinetics of lamotrigine co-administered with valproic acid in Chinese epileptic children using nonlinear mixed effects modeling

The LTG PPK model developed in this study could be useful for individualizing LTG dosage regimens in pediatric patients receiving combination therapy, especially therapy that includes VPA.

Influence of genetic variants and antiepileptic drug co-treatment on lamotrigine plasma concentration in Mexican Mestizo patients with epilepsy

Co-treatment with VPA was the most significant factor influencing LTG plasma concentration, followed by UGT1A4*1b , and that patients carrying UGT2B7 c.-161T required higher LTG daily doses, provide valuable information for the clinical use of LTG in MM patients with epilepsy.

Frequencies of UGT1A4*2 (P24T) and *3 (L48V) and their effects on serum concentrations of lamotrigine

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, and suggested the *2 variant was associated with a trend towards higher serum concentrations, while the *3 variant wasassociated with significantly lower serum concentrations.

Influence of the UGT2B7 -161C>T polymorphism on the population pharmacokinetics of lamotrigine in Thai patients

The use of enzyme inducers, valproic acid, and the UGT2B7-161 C>T SNP were found to significantly influence lamotrigine apparent clearance (CL/F) and the model presented here could be useful for lamotigine dose adjustment in clinical practice.

Relationship Between UGT1A4 and UGT2B7 Polymorphisms and the Steady-State Plasma Concentrations of Lamotrigine in Patients With Treatment-Resistant Depressive Disorder Receiving Lamotrigine as Augmentation Therapy

This study suggests that genetic polymorphisms that affect enzyme activities of UGTs do not affect the Css of lamotrigine in patients with treatment-resistant depressive disorder receiving lamotigine as augmentation therapy.

Association of polymorphisms in EPHX1, UGT2B7, ABCB1, ABCC2, SCN1A and SCN2A genes with carbamazepine therapy optimization.

The present study identified genetic factors associated with CBZ Therapy optimization and provided useful information for individualized CBZ therapy in epileptic patients.



The Impact of UGT1A8, UGT1A9, and UGT2B7 Genetic Polymorphisms on the Pharmacokinetic Profile of Mycophenolic Acid After a Single Oral Dose in Healthy Volunteers

After a single oral dose of MMF in healthy volunteers, specific UGT genotypes significantly alter MPA PKs and this clearly warrants additional studies with complete and detailed genetic profiling of UGT 1A8, UGT1A9, and UGT2B7 genes.

Influence of UGT1A8 and UGT2B7 genetic polymorphisms on mycophenolic acid pharmacokinetics in Japanese renal transplant recipients

Both UGT1A8 and UGT2B7 allelic variants seem not to affect Japanese interindividual variability for plasma MPA concentration, and the absorption of MPA through enterohepatic recirculation is higher at night.

AcylMPAG Plasma Concentrations and Mycophenolic Acid-Related Side Effects in Patients Undergoing Renal Transplantation Are Not Related to the UGT2B7-840G>A Gene Polymorphism

No influence of the −840G>A UGT2B7 SNP on AcylMPAG exposure in patients undergoing renal transplantation is found and there also was no association between this variant genotype and the incidence of diarrhea or leucopenia, two adverse events for which a role for Ayl-glucuronide metabolite has been suggested.

Genetic susceptibility to diclofenac-induced hepatotoxicity: contribution of UGT2B7, CYP2C8, and ABCC2 genotypes.

Allelic variants of UGT2B7, CYP2C8, and ABCC2, which may predispose to the formation and accumulation of reactive diclofenac metabolites are associated withdicl ofenac hepatotoxicity.

Pharmacokinetic and Pharmacodynamic Interaction of Lorazepam and Valproic Acid in Relation to UGT2B7 Genetic Polymorphism in Healthy Subjects

It is suggested that the UGT2B7 genotype probably affects lorazepam–valproate pharmacodynamic interaction, especially in subjects who have homovariant genotypes of UGT3B7 and UGT1B15, although the effects on the pharmacokinetics are less significant.

Polymorphisms of UDP-glucuronosyltransferase gene and irinotecan toxicity: a pharmacogenetic analysis.

It is suggested that determination of the UGT1A1 genotypes might be clinically useful for predicting severe toxicity by irinotecan in cancer patients and warrants a prospective trial to corroborate the usefulness of gene diagnosis of UGT2A1 polymorphisms prior tb irinOTecan chemotherapy.

Lamotrigine serum concentration-to-dose ratio: influence of age and concomitant antiepileptic drugs and dosage implications.

The LTG C/D ratio was 10 times lower in patients receiving LTG and inducers than in those receivingLTG and VPA (in both children and adults), and this difference was higher than the four-fold difference described for LTG half-life and the two-fold differences currently used in LTG dosage.

Influence of Nonsynonymous Polymorphisms of UGT1A8 and UGT2B7 Metabolizing Enzymes on the Formation of Phenolic and Acyl Glucuronides of Mycophenolic Acid

Several UGT1A8 variants identified may potentially account for the large interindividual variance in MMF pharmacokinetics and deserve further clinical investigations.

The influence of dosage, age, and comedication on steady state plasma lamotrigine concentrations in epileptic children: a prospective study with preliminary assessment of correlations with clinical response.

It is shown that plasma LTG concentrations exhibit a wide interindividual variability under the influence of age and type of comedication, but they are predictably related to dosage within individual patients.