Impact of NR1I2, adenosine triphosphateebinding cassette transporters genetic polymorphisms on the pharmacokinetics of ginsenoside compound K in healthy Chinese volunteers

Luping Zhou; Lulu Chen; Yaqin Wang; Jie Huang; Guoping Yang; Zhirong Tan; Yicheng Wang; Jianwei Liao; Gan Zhou; Kai Hu; Zhenyu Li; Dongsheng Ouyang

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저자정보: Luping Zhou (Central South University) Lulu Chen (Central South University) Yaqin Wang (Central South University) Jie Huang (Central South University) Guoping Yang (Central South University) Zhirong Tan (Central South University) Yicheng Wang (Central South University) Jianwei Liao (Central South University) Gan Zhou (Central South University) Kai Hu (Central South University) Zhenyu Li (Central South University) Dongsheng Ouyang (Central South University)

저널정보: 고려인삼학회 Journal of Ginseng Research Journal of Ginseng Research Vol.43 No.3

발행연도: 2019.6

수록면: 460 - 474 (15page)

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Background: Ginsenoside compound K (CK) is a promising drug candidate for rheumatoid arthritis. This study examined the impact of polymorphisms in NR1I2, adenosine triphosphateebinding cassette (ABC) transporter genes on the pharmacokinetics of CK in healthy Chinese individuals.
Methods: Forty-two targeted variants in seven genes were genotyped in 54 participants using Sequenom MassARRAY system to investigate their association with major pharmacokinetic parameters of CK and its metabolite 20(S)-protopanaxadiol (PPD). Subsequently, molecular docking was simulated using the AutoDock Vina program.
Results: ABCC4 rs1751034 TT and rs1189437 TT were associated with increased exposure of CK and decreased exposure of 20(S)-PPD, whereas CFTR rs4148688 heterozygous carriers had the lowest maximum concentration (Cmax) of CK. The area under the curve from zero to the time of the last quantifiable concentration (AUClast) of CK was decreased in NR1I2 rs1464602 and rs2472682 homozygous carriers, while Cmax was significantly reduced only in rs2472682. ABCC4 rs1151471 and CFTR rs2283054 influenced the pharmacokinetics of 20(S)-PPD. In addition, several variations in ABCC2, ABCC4, CFTR, and NR1I2 had minor effects on the pharmacokinetics of CK. Quality of the best homology model of multidrug resistance protein 4 (MRP4) was assessed, and the ligand interaction plot showed the mode of interaction of CK with different MRP4 residues.
Conlusion: ABCC4 rs1751034 and rs1189437 affected the pharmacokinetics of both CK and 20(S)-PPD. NR1I2 rs1464602 and rs2472682 were only associated with the pharmacokinetics of CK. Thus, these hereditary variances could partly explain the interindividual differences in the pharmacokinetics of CK.

#Genetic polymorphisms #Ginsenoside compound K #Pharmacokinetics #Transporters

참고문헌 (63)

참고문헌 신청

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