Journal of Pharmaceutical Investigation

  • 제37권6호
  • /
  • Pages.369-376
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  • 2007
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  • 2093-5552(pISSN)
  • /
  • 2093-6214(eISSN)
한국약제학회 (The Korean Society of Pharmaceutical Sciences and Technology)
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면역억제제의 약물속도론적/약력학적 파라미터에 기초한 표현형과 유전형의 상관성

Phenotype Based on Pharmacokinetic/Pharmacodynamic Parameters and Genotype Correlations of Immunosupressants

  • 이용복 (전남대학교 약학대학 부속 생물학적동등성 및 가교시험연구소) ;
  • 조혜영 (약리연구부, 국립독성과학원/식품의약품안전청)
  • Lee, Yong-Bok (College of Pharmacy and Institute of Bioequivalence and Bridging Study, Chonnam National University) ;
  • Cho, Hea-Young (Pharmacological Research Department, NITR, KFDA)
  • 발행 : 2007.12.21
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초록

Cyclosporine (CsA) and tacrolimus (FK506) have a narrow therapeutic range, and their pharmacokinetic (PK) characteristic varies among individual. They are also substrates for cytochrome P450 (CYP) 3A4, 3A5 genes, and P-glycoprotein, the product of the multidrug resistance 1 (MDR1). The aims were to investigate the relationship between CYP3A and MDR1 genotypes and their PK parameters among healthy subjects. We investigated the genotype for CYP3A and MDR1 gene in human using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. After oral administration of CsA and FK506 (100 mg and 1 mg, respectively), whole blood samples were taken up to 24 hours. Blood CsA and FK506 concentrations were measured by LC/MS/MS. Each PK parameters were compared using Kruskal-Wallis test according to the CYP3A and MDR1 genotype. We found that the values of AVC for CsA were significantly different among CYP3A5 and MDR1 exon 26 (C3435T) genotypes (P=0.037 and P=0.049). On the other hand, the AUC for FK506 was significantly different only among CYP3A5 genotypes (P=0.013). The results clearly demonstrate the effects of CYP3A5 and MDR1 exon 26 on Cys and FK506 disposition.

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