The influence of UGT2B7 genotype on valproic acid pharmacokinetics in Chinese epilepsy patients

@article{Sun2015TheIO,
  title={The influence of UGT2B7 genotype on valproic acid pharmacokinetics in Chinese epilepsy patients},
  author={Yinhua Sun and Wen-Yan Zhuo and Hong Lin and Zhengkang Peng and Hua-ming Wang and Hao-wu Huang and Yu-hong Luo and Fa-qing Tang},
  journal={Epilepsy Research},
  year={2015},
  volume={114},
  pages={78-80}
}
Impact of Age and Genotype on Serum Concentrations of Valproic Acid and Its Hepatotoxic Metabolites in Chinese Pediatric Patients with Epilepsy.
TLDR
It is suggested that UGT2B7 802C>T polymorphism and age are factors affecting the concentrations of dose-adjusted VPA and its metabolites, and careful administration is particularly necessary for younger patients who are UGT1A6 and 802C >T poor metabolizers.
Influence of UGT2B7 and UGT1A6 polymorphisms on plasma concentration to dose ratio of valproic acid in Chinese epileptic children
TLDR
This research indicated that UGT2B7 rs7668258 (C>T) and UGT1A6 rs2070959 (A>G) polymorphisms may be correlated to the normalised plasma concentrations of VPA in Chinese epileptic children.
UGT1A6 and UGT2B7 Gene Polymorphism and its Effect in Pediatric Epileptic Patients on Sodium Valproate Monotherapy
TLDR
Though there was a difference in pattern of gene polymorphism with concerning UGT1A6 and UGT2B7, however, it has not contributed to variation in serum concentration of sodium valproate in the present study population.
Association of UGT2B7 and UGT1A4 Polymorphisms with Serum Concentration of Antiepileptic Drugs in Children
TLDR
UGT2B7, UGT1A4 polymorphisms play crucial roles in metabolism of VPA and LTG in epileptic children and multiple linear regression analysis revealed that VPA or LTG adjusted concentration showed a good linear relation with sex and age.
Influence of acylpeptide hydrolase polymorphisms on valproic acid level in Chinese epilepsy patients.
TLDR
APEH polymorphism has significant influence on VPA pharmacokinetics in Chinese population and is still obvious when stratified by UGT2B7 rs7668258 polymorphism.
Effect of UGT2B7 genotypes on plasma concentration of valproic acid: a meta-analysis
TLDR
The results of this meta-analysis demonstrated that UGT2B7 G211T and C161T polymorphisms were able to affect the pharmacokinetics in epilepsy patients treated with VPA, which provide further evidence for genetic effects of UGT 2B7 gene on pharmacokinetic and pharmacodynamics of VPA.
Genetic polymorphisms and valproic acid plasma concentration in children with epilepsy on valproic acid monotherapy
Effects of UGT1A6 and GABRA1 on Standardized Valproic Acid Plasma Concentrations and Treatment Effect in Children With Epilepsy in China
TLDR
The findings may help clinicians to adjust the dose and predict treatment effect for children with epilepsy receiving VPA treatment and was associated with an increase in NCVPA.
...
...

References

SHOWING 1-10 OF 14 REFERENCES
Influence of UDP-glucuronosyltransferase polymorphisms on valproic acid pharmacokinetics in Chinese epilepsy patients
TLDR
The results suggest that UGT1A3*5 may be an important determinant of individual variability in the pharmacokinetics of VPA and that it may be necessary to increase VPA dose for UGT2B7 carriers to ensure its therapeutic range of 50–100 μg/mL.
Pharmacokinetic and Pharmacodynamic Interaction of Lorazepam and Valproic Acid in Relation to UGT2B7 Genetic Polymorphism in Healthy Subjects
TLDR
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.
Distribution of UGT1A9 C-2152T and UGT2B7 G211T mutants in Chinese Han population
TLDR
A straightforward and prompt PCR-RFLP assay has a good reproducibility, and therefore can be used to genotype for the UGT2B7 G211T polymorphism in a large population samples and is high in a Chinese population.
An association of UDP-glucuronosyltransferase 2B7 C802T (His268Tyr) polymorphism with bladder cancer in benzidine-exposed workers in China.
TLDR
This study points for the first time to an association between a homozygous mutant genotype of human UDP-glucuronosyltransferase 2B7 catalyzing the biotransformation of benzidine and an elevated bladder cancer risk for formerly benzidine-exposed workers of the dyestuff industry.
Effect of Aging on Glucuronidation of Valproic Acid in Human Liver Microsomes and the Role of UDP-Glucuronosyltransferase UGT1A4, UGT1A8, and UGT1A10
TLDR
This investigation revealed no differences in VPAG formation in younger versus elderly HMLs and revealed three other UGTs that form VPAGs in vitro, the first reported activity of these UGTS toward VPA glucuronidation.
Urinary Excretion of Valproate and Some Metabolites in Chronically Treated Patients
TLDR
The wide variation in the patterns of urinary metabolite excretion precludes use of routinely collected urinary excretion data as a basis for detecting any but severe noncompliance with VPA therapy or abnormalities of VPA metabolism.
Urinary excretion of valproate metabolites in children and adolescents.
TLDR
Older children and adolescents, when compared with younger children, and those comedicated with LTG excrete a higher proportion of VPA dose as VPA-glucuronide.
Clinically relevant drug interactions with antiepileptic drugs.
  • E. Perucca
  • Medicine, Biology
    British journal of clinical pharmacology
  • 2006
TLDR
Some patients with difficult-to-treat epilepsy benefit from combination therapy with two or more antiepileptic drugs (AEDs), and pharmacodynamic interactions involving AEDs have not been well characterized, but their understanding is important for a more rational approach to combination therapy.
MECHANISM OF THE DRUG INTERACTION BETWEEN VALPROIC ACID AND CARBAPENEM ANTIBIOTICS IN MONKEYS AND RATS
TLDR
Results clearly indicate one of the important causes of drug interaction as follows: carbapenems would inhibit the hydrolytic enzyme, which is involved in the Hydrolysis of VPA-G to VPA, resulting in a decrease of plasma concentration of V PA.
Clinical Pharmacokinetics of Valproic Acid — 1988
TLDR
Sodium valproic acid has been widely used in the last decade and is now considered a relatively safe and effective anticonvulsant agent and its use in the treatment of anxiety, alcoholism and mood disorders, although these indications require further clinical studies.
...
...