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ABCB1 polymorphisms may have a minor effect on ciclosporin blood concentrations in myasthenia gravis patients
Zhang, Ya-tong1,2; Yang, Li-ping2; Shao, Hong1; Li, Ke-xin2; Sun, Chun-hua2; Shi, Lu-wen1
关键词ABCB1 myasthenia gravis ciclosporin pharmacogenomics single nucleotide polymorphism blood concentrations
刊名BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
2008-08-01
DOI10.1111/j.1365-2125.2008.03180.x
66期:2页:240-246
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Pharmacology & Pharmacy
研究领域[WOS]Pharmacology & Pharmacy
关键词[WOS]SINGLE-NUCLEOTIDE POLYMORPHISMS ; P-GLYCOPROTEIN MDR1 ; GENETIC-POLYMORPHISM ; HAPLOTYPES ; EXPRESSION
英文摘要

AIMS

Ciclosporin (CsA), which is widely used in autoimmune disease and transplantation, has a narrow therapeutic index. It also shows considerable interindividual variability in its pharmacokinetics, which may be attributable to polymorphisms of the multidrug efflux pump P-glycoprotein, encoded by MDR-1. The aim was to determine the role of genetic polymorphisms in MDR-1 with respect to interindividual variability of CsA blood concentrations in myasthenia gravis (MG) patients.

METHODS

MG patients (n = 129) receiving CsA were genotyped for MDR-1 1236C-->T (exon 12), 2677G-->T (exon 21) and 3435C-->T (exon 26). Trough blood and peak blood concentrations were determined to see if there was correlation with the corresponding genotype.

RESULTS

We observed a trend for CsA blood concentrations, especially peak blood concentrations, to be higher with the wild-type allele compared with minor alleles in genotype and haplotype. Furthermore, under the same CsA regimen, it was found that the trough concentrations of variant genotype (ABCB1 1236TT or ABCB1 2677TT) were significant greater than those of wild-type (ABCB1 1236CC or ABCB1 2677GG, respectively) (P = 0.0222 and 0.0081). The trough concentrations of wild-type haplotype pair group were significantly lower those that of the mutant type pair group (TT-TT-TT) (P = 0.007).

CONCLUSIONS

ABCB1 polymorphisms in both genotype and haplotype may have a minor effect on the CsA blood concentrations.

语种英语
WOS记录号WOS:000257633000010
引用统计
被引频次:13[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61833
专题北京大学药学院
作者单位1.Beijing Hosp, Dept Pharm, Beijing, Peoples R China
2.Peking Univ, Sch Pharmaceut Sci, Dept Pharm Adm & Clin Pharm, Beijing 100083, Peoples R China
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GB/T 7714
Zhang, Ya-tong,Yang, Li-ping,Shao, Hong,et al. ABCB1 polymorphisms may have a minor effect on ciclosporin blood concentrations in myasthenia gravis patients[J]. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY,2008,66(2):240-246.
APA Zhang, Ya-tong,Yang, Li-ping,Shao, Hong,Li, Ke-xin,Sun, Chun-hua,&Shi, Lu-wen.(2008).ABCB1 polymorphisms may have a minor effect on ciclosporin blood concentrations in myasthenia gravis patients.BRITISH JOURNAL OF CLINICAL PHARMACOLOGY,66(2),240-246.
MLA Zhang, Ya-tong,et al."ABCB1 polymorphisms may have a minor effect on ciclosporin blood concentrations in myasthenia gravis patients".BRITISH JOURNAL OF CLINICAL PHARMACOLOGY 66.2(2008):240-246.
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