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- W2339100142 abstract "BackgroundEpilepsy is a common chronic neurological condition that is characterized by recurrent unprovoked seizures.The 1236C>T SNP is synonymous polymorphismof the multidrug resistant 1 (MDR1) gene, which encodes the major transmembrane efflux transporter P-glycoprotein and form an important class of proteins for regulating pharmacokinetics. Phenytoin, a widely used anti-epileptic drug, exhibits marked inter-individual variation in Pharmacokinetics and attributed to genetic factors such as MDR1 polymorphism.ObjectiveThe present study was undertaken to investigate the influence of MDR1 variant genotypes on Phenytoin Pharmacokinetics in the epileptic patients from Saudi Arabia.Material and Methods25 epileptic individuals with non-responders to phenytoin monotherapy and 25 epileptic subjects with responders tophenytoin monotherapywere recruited after getting their informed consent and genotyped for MDR1 (1236C>T) polymorphisms by Polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP Method).Allele frequencies were derived from genotypic data Phenytoin plasma levels were analyzed by reverse phase HPLC method and Pharmacokinetic parameters were estimated by non-compartmental analysis using PK solutions software.ResultsThe MDR1 1236C>T showed a significant allelic association and genotypic association between non responders and responders to phenytoin (P<0.01). The pharmacokinetics parameters in homozygous mutant group showed longer half-life (t1/2 = 32.26 hrs) and less clearance rate (CL = 0.41 L/hr) when compared to wild type group (t 1/2 = 18.2hrs, CL = 0.7 L/hr).Conclusion:Our finding suggest that the MDR1 genetic polymorphism influences Phenytoin Pharmacokinetics. So the therapeutic outcome of MDR1 (1236C>T) genotype together with pharmacokinetic measurements might be useful in the context of improving the individualized efficacy of therapy in non-responders to phenytoin. Disclosure: Dr. Alhazzani has nothing to disclose. Dr. Munisamy has nothing to disclose. Dr. Karunakaran has nothing to disclose." @default.
- W2339100142 created "2016-06-24" @default.
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- W2339100142 date "2016-04-05" @default.
- W2339100142 modified "2023-09-24" @default.
- W2339100142 title "Pharmacogenetics of ATP Binding Cassette Transporter - MDR1 Gene Polymorphism (MDR1 - 1236C>T Polymorphism) and Response to Antiepileptic Drug Phenytoin Pharmacokinetics in Epilepsy (P2.046)" @default.
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