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RISS 인기검색어
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- 저자 : Dongsheng Ouyang (검색결과 2 건)
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Luping Zhou,Lulu Chen,Yaqin Wang,Jie Huang,Guo Ping Yang,Zhi-Rong Tang,Yicheng Wang,Jianwei Liao,Gan Zhou,Kai-hua Wei,Zhenyu Li,Dongsheng Ouyang 고려인삼학회 2019 Journal of Ginseng Research Vol.43 No.3
Background: Ginsenoside compound K (CK) is a promising drug candidate for rheumatoid arthritis. Thisstudy 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 SequenomMassARRAY system to investigate their association with major pharmacokinetic parameters of CK and itsmetabolite 20(S)-protopanaxadiol (PPD). Subsequently, molecular docking was simulated using theAutoDock Vina program. Results: ABCC4 rs1751034 TT and rs1189437 TT were associated with increased exposure of CK anddecreased exposure of 20(S)-PPD, whereas CFTR rs4148688 heterozygous carriers had the lowestmaximum concentration (Cmax) of CK. The area under the curve from zero to the time of the lastquantifiable concentration (AUClast) of CK was decreased in NR1I2 rs1464602 and rs2472682 homozygouscarriers, while Cmax was significantly reduced only in rs2472682. ABCC4 rs1151471 and CFTR rs2283054influenced the pharmacokinetics of 20(S)-PPD. In addition, several variations in ABCC2, ABCC4, CFTR, andNR1I2 had minor effects on the pharmacokinetics of CK. Quality of the best homology model of multidrugresistance protein 4 (MRP4) was assessed, and the ligand interaction plot showed the mode of interactionof 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, thesehereditary variances could partly explain the interindividual differences in the pharmacokinetics of CK.
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Zhou, Luping,Chen, Lulu,Wang, Yaqin,Huang, Jie,Yang, Guoping,Tan, Zhirong,Wang, Yicheng,Liao, Jianwei,Zhou, Gan,Hu, Kai,Li, Zhenyu,Ouyang, Dongsheng The Korean Society of Ginseng 2019 Journal of Ginseng Research Vol.43 No.3
Background: Ginsenoside compound K (CK) is a promising drug candidate for rheumatoid arthritis. This study examined the impact of polymorphisms in NR1I2, adenosine triphosphate-binding 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 ($C_{max}$) of CK. The area under the curve from zero to the time of the last quantifiable concentration ($AUC_{last}$) of CK was decreased in NR1I2 rs1464602 and rs2472682 homozygous carriers, while $C_{max}$ 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.
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