title: ABCB1 polymorphisms may have a minor effect on ciclosporin blood concentrations in myasthenia gravis patients.
abstract: OBJECTIVE
  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.
authors: Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Science, Peking University, Bejing, China.
authors: Ya-tong
authors: YT
authors: Zhang
authors: Li-ping
authors: LP
authors: Yang
authors: Hong
authors: H
authors: Shao
authors: Ke-xin
authors: KX
authors: Li
authors: Chun-hua
authors: CH
authors: Sun
authors: Lu-wen
authors: LW
authors: Shi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D016572:Cyclosporine / Q000097:blood / Q000493:pharmacokinetics*; D005091:Exons / Q000235:genetics; D005260:Female; D019450:Genes, MDR / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011237:Predictive Value of Tests
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016572:Cyclosporine