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Effect of MDR1 C1236T polymorphism on cyclosporine pharmacokinetics: A systematic review and meta-analysis

Zhe Chen1, Lingli Zhang, Chunsong Yang

  • 1Department of Pharmacy, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, Sichuan Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, Sichuan West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, China.

Medicine
|February 1, 2018
PubMed

Insights

The MDR1 C1236T polymorphism may slightly impact cyclosporine pharmacokinetics. This meta-analysis found minor effects on drug concentrations in transplantation patients, influencing trough blood concentration (C0) and 2-hour levels (C2).

Area of Science:

  • Pharmacogenomics
  • Drug Metabolism
  • Immunosuppression

Background:

  • Cyclosporine (CsA) pharmacokinetics exhibit significant inter-individual variability.
  • Conflicting data exist regarding the influence of MDR1 exon 12 SNP C1236T on CsA pharmacokinetics.
  • This meta-analysis aims to clarify the association between MDR1 C1236T polymorphism and CsA pharmacokinetics.

Purpose of the Study:

  • To investigate the effect of the MDR1 C1236T single nucleotide polymorphism (SNP) on cyclosporine pharmacokinetics.
  • To resolve conflicting findings in existing literature regarding this genetic association.
  • To provide a comprehensive analysis of SNP C1236T's impact on CsA drug levels.

Main Methods:

  • A systematic literature search was performed across multiple databases (PubMed, Embase, Cochrane Library, CNKI, Wan Fang, CBM, VIP) up to January 2017.
  • Pharmacokinetic parameters including C0, C2, Cmax, and daily dose were extracted from eligible studies.
  • A meta-analysis was conducted using RevMan 5.3 software to synthesize the data.

Main Results:

  • Eleven studies encompassing 1361 individuals were included in the meta-analysis.
  • Significant differences in dose-adjusted C0 were observed between CC and TT genotypes (P=.02).
  • Significant differences in C2 levels were found between CC and CT genotypes (P=.03), and between CC and TT genotypes (P=.03).
  • No major influence was detected on Cmax, daily dose, or C0 (unadjusted).

Conclusions:

  • The MDR1 C1236T polymorphism appears to have a minor effect on cyclosporine pharmacokinetics.
  • This genetic variation may influence specific pharmacokinetic parameters like C0 and C2 in transplantation patients.
  • Further research may be warranted to fully elucidate the clinical significance of this SNP in CsA therapy.
Abstract

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