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学科主题: 药学
题名:
ABCB1 polymorphisms may have a minor effect on ciclosporin blood concentrations in myasthenia gravis patients
作者: 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
发表日期: 2008-08-01
DOI: 10.1111/j.1365-2125.2008.03180.x
卷: 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
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61833
Appears in Collections:北京大学药学院_期刊论文

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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

Recommended Citation:
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.
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