The Effect ofMDR1 G2677T/A polymorphism on pharmacokinetics of gabapentin in healthy Korean subjects

Abstract

This study evaluated the relationship between the genetic polymorphism in the MDR1 (exon 21) genes and the pharmacokinetics of gabapentin (GBP) in healthy Korean subjects. The healthy Koreans were genotyped with respect to MDR1 (exon 21, 30 subjects) using polymerase chain reaction-based diagnostic testing. The pharmacokinetic profile of GBP was examined. A single oral dose of 300 mg GBP in a capsule was administered to the subjects and the blood samples were taken during a 24 h post-dose interval. The serum GBP concentration was measured using an HPLC-fluorescence detector system. There were no significant (P < 0.05) differences between the genotypes and pharmacokinetic parameters such as AUC(0-1h), AUC(0-1.5h), AUC(0-infinity), Cmax and t1/2. However, there was a trend toward higher values of the absorptive phase characterized by the AUC(0-1h) and AUC(0-1.5h) in 2677T/A subjects. In conclusion, this study suggests that GBP may be a weak substrate for the P-glycoprotein (P-gp) transporter.

Pharmacogenetics‐based population pharmacokinetic analysis of gabapentin in patients with chronic pain: Effect of OCT2 and OCTN1 gene polymorphisms

“…Few studies about the influence of ABCB1 expression in GAB PK are available. 35,40 The polymorphism 2677G>T/A of ABCB1 gene was recently correlated with increase in k a of GAB. Although LAT2 transporter activity has been associated with GAB absorption, its gene (SLC7A8) is highly conserved and there are no studies showing that polymorphisms could change gene expression or transporter function.…”

“…Another limitation is that genetic polymorphisms related to absorption process were not evaluated as covariates. Few studies about the influence of ABCB1 expression in GAB PK are available . The polymorphism 2677G>T/A of ABCB1 gene was recently correlated with increase in k a of GAB.…”

Different Transport Activity of Human Triallelic MDR1893Ala/Ser/Thr Variant and its Association with Herb Extracts

“…Among the variants, nonsynonymous rs2032582 (2677G/T/A; 893Ala/Ser/Thr) in exon 22 is a triallelic variant that has been implicated as a risk factor for diseases (e.g. obesity, colorectal cancer) (Osswald et al, 2007;Ichihara et al, 2008;Osswald et al, 2007) and as a modifying factor of pharmacokinetics and clinical response to drugs (Kang et al, 2007;Kato et al, 2008).…”

“…The overexpression of MDR1 causes multidrug resistance in clinical tumors and is related to the prognosis of cancers in patients (Kang et al , ; Wuchter et al , ). Diverse pharmacological compounds, such as cardiac drugs (e.g.…”

Pharmacogenetics of Chronic Pain and Its Treatment

“…Change in gabapentin's disposition due to 2677T/A MDR1/ABCB1 alleles was less pronounced resulting only in trend toward higher values of the absorptive phase characterized by the AUC (0-1 h) and AUC (0–1.5 h) [88]. …”