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

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

British journal of clinical pharmacology (2008-08-23)
Ya-tong Zhang, Li-ping Yang, Hong Shao, Ke-xin Li, Chun-hua Sun, Lu-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 lower those that of the mutant type pair group (TT-TT-TT) (P = 0.007). ABCB1 polymorphisms in both genotype and haplotype may have a minor effect on the CsA blood concentrations.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Mdr1b Rat, membrane preparation for ATPase Assays, recombinant, expressed in baculovirus infected Sf9 cells
Sigma-Aldrich
SB-MDR1-Hi5-PREDEASY-ATPase kit, membrane based kit for Human MDR1 ATPase Transport Assays