ABCB1 polymorphisms may have a minor effect on ciclosporin blood concentrations in myasthenia gravis patients.

British Journal of Clinical Pharmacology
Ya-tong ZhangLu-wen Shi

Abstract

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. 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. 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 low...Continue Reading

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Citations

Mar 11, 2010·Pharmacogenetics and Genomics·Laura M HodgesRuss B Altman
Jun 30, 2011·Human Genomics·Ogechi IkediobiLouise Warnich
Apr 4, 2015·International Journal of Antimicrobial Agents·Jessica CusatoAntonio D'Avolio
Feb 11, 2015·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Jessica CusatoAntonio D'Avolio
Mar 7, 2018·The Journal of Antimicrobial Chemotherapy·Jessica CusatoAntonio D'Avolio
Apr 28, 2018·Clinical and Experimental Pharmacology & Physiology·Xingang LiNing Ma
Aug 24, 2017·Journal of Clinical Pharmacy and Therapeutics·Y PradoL A Salazar
Oct 15, 2018·Molecular Biology Reports·Alma Faviola Favela-MendozaMarisol López-López

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