The effect of MDR1 G2677T/A polymorphism on pharmacokinetics of gabapentin in healthy Korean subjects.
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.
Kang
Hyun-Ah
HA
College of Pharmacy and Institute of Bioequivalence and Bridging Study, Chonnam National University, Gwangju 500-757, Korea.
Cho
Hea-Young
HY
Lee
Yong-Bok
YB
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000225:Adenine; D000284:Administration, Oral; D000328:Adult; D000588:Amines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D044466:Asian People; D002214:Capsules; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003509:Cyclohexanecarboxylic Acids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005091:Exons; D000077206:Gabapentin; D005838:Genotype; D006147:Guanine; D006207:Half-Life; D006801:Humans; D007723:Korea; D008297:Male; D008657:Metabolic Clearance Rate; D010641:Phenotype; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D015203:Reproducibility of Results; D013941:Thymine; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000588:Amines; D000927:Anticonvulsants; D002214:Capsules; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D006147:Guanine; D000077206:Gabapentin; D000225:Adenine; D013941:Thymine