ABCC2 c.-24 C>T single-nucleotide polymorphism was associated with the pharmacokinetic variability of deferasirox in Chinese subjects.
Purpose: Our aim was to evaluate the influence of genetic polymorphisms involved in the metabolism and transportation of deferasirox on deferasirox pharmacokinetics in the Chinese population. Methods: Thirty-eight healthy Chinese subjects were administered with a single dose of 20 mg kg−1 deferasiro...
| Publicado en: | European Journal of Clinical Pharmacology Vol. 76; no. 1; pp. 51 - 60 |
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| Autores principales: | , , , , , , , , , , |
| Formato: | research tables/charts Journal Article |
| Publicado: |
Springer Nature
Jan2020
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=141211412&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 141211412 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00316970 NP9 jtl: European Journal of Clinical Pharmacology issn: 00316970 maglogo: N pubinfo: dt: Jan2020 vid: 76 iid: 1 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 141211412 141211412 141211412 10.1007/s00228-019-02775-1 141211412 ppf: 51 ppct: 9 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: ABCC2 c.-24 C>T single-nucleotide polymorphism was associated with the pharmacokinetic variability of deferasirox in Chinese subjects. aug: au: Cao, Kangna Ren, Guanghui Lu, Chengcan Wang, Yao Tan, Yanan Zhou, Jing Zhang, Yongjie Lu, Yang Li, Ning Chen, Xijing Zhao, Di affil: Clinical Pharmacokinetics Laboratory, China Pharmaceutical University, #639 Longmian Avenue, Jiangning District, 211198, Nanjing, China sug: subj: Carrier Proteins Polymorphism, Genetic Benzene Derivatives Pharmacokinetics Benzene Derivatives Metabolism Pharmacogenetics Human China Benzene Derivatives Administration and Dosage Benzene Derivatives Blood Alleles Chromatography, Liquid Mass Spectrometry Descriptive Statistics ab: Purpose: Our aim was to evaluate the influence of genetic polymorphisms involved in the metabolism and transportation of deferasirox on deferasirox pharmacokinetics in the Chinese population. Methods: Thirty-eight healthy Chinese subjects were administered with a single dose of 20 mg kg−1 deferasirox. Allelic discriminations for eight single-nucleotide polymorphisms (SNPs) in UDP-glucuronosyltransferase 1A1, 1A3 (UGT1A1, UGT1A3), multidrug resistance protein 2 (MRP2, ABCC2), and breast cancer resistance protein (BCRP, ABCG2) were performed. The concentrations of deferasirox in the plasma were determined by UPLC-MS/MS. Results: Subjects carrying ABCC2 c.-24 T allele had a 65% higher clearance (CL/F) and 42% lower area under the concentration–time curve from 0 to 72 h (AUC0-72h) as compared with non-carriers (P = 0.008, P = 0.011, respectively). ABCC2 c.-24 T was also associated with 59% shorter half-life (T1/2) and 17% shorter mean residence time (MRT) (P = 0.030, P = 0.014, respectively). ABCC2 1249A was associated with a marginal increase in deferasirox Cmax (P = 0.07). Genetic polymorphisms of UGT1A1, UGT1A3, and ABCG2 did not significantly influence the pharmacokinetics of deferasirox. Subjects with UGT1A1 211GG-(-1352)CC-(-3156)GG haplotype had higher AUC0-72h than others. Since only two subjects were recruited in the GG-CC-GG group, further confirmative studies were warranted. Conclusions: ABCC2 c.-24 C>T was associated with the pharmacokinetic variability of deferasirox in Chinese subjects. This study revealed an important role of MRP2 in the pharmacokinetics of deferasirox and drew attention to drug combination with MRP2 inhibitors like cyclosporine and methotrexate in deferasirox therapy. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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