MDR1 haplotypes derived from exons 21 and 26 do not affect the steady-state pharmacokinetics of tacrolimus in renal transplant patients

被引:68
作者
Mai, I
Perloff, ES
Bauer, S
Goldammer, M
Johne, A
Filler, G
Budde, K
Roots, I
机构
[1] Charite Univ Med Berlin, Inst Clin Pharmacol, D-10098 Berlin, Germany
[2] Charite Univ Med Berlin, Dept Internal Med & Nephrol, D-10098 Berlin, Germany
[3] Univ Ottawa, Childrens Hosp Eastern Ontario, Dept Pediat, Div Pediat Nephrol, Ottawa, ON K1N 6N5, Canada
关键词
P-glycoprotein; MDR1; haplotype; tacrolimus; pharmacokinetics; patients;
D O I
10.1111/j.1365-2125.2004.02182.x
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aim This retrospective study investigated the influence of MDR1 haplotypes derived from the polymorphisms 2677G > T (exon 21) and 3435C > T (exon 26) on the pharmacokinetics of the immunosuppressant drug tacrolimus in 73 renal transplant patients. Methods Based on both variants of SNPs 2677 and 3435, four different haplotypes and eight different genotypes were identified in the study sample. Tacrolimus trough concentrations (C-0) were compared between different SNP variants and genotypes, as well as between carriers and noncarriers of each haplotype. Additionally, CYP3A5 genotype (6956G > A) was determined. Results No significant differences were observed between groups. Differences in mean tacrolimus C-0 values between carriers and noncarriers of each haplotype ranged from -0.04 mug/litre (95% confidence interval: -0.53 to 0.60) to -23 mug/litre (-1.07 to 1.53). No association was found between CYP3A5*1/*3 genotype and tacrolimus Co concentractions. Conclusion MDR1 haplotypes derived from the SNPs 2677G > T (exon 21) and 3435C > T (exon 26) do not influence the pharmacokinetics of tacrolimus in renal transplant patients.
引用
收藏
页码:548 / 553
页数:6
相关论文
共 27 条
[21]   Impact of St John's wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients [J].
Mai, I ;
Störmer, E ;
Bauer, S ;
Krüger, H ;
Budde, K ;
Roots, I .
NEPHROLOGY DIALYSIS TRANSPLANTATION, 2003, 18 (04) :819-822
[22]   A common P-glycoprotein polymorphism is associated with nortriptyline-induced postural hypotension in patients treated for major depression [J].
Roberts R.L. ;
Joyce P.R. ;
Mulder R.T. ;
Begg E.J. ;
Kennedy M.A. .
The Pharmacogenomics Journal, 2002, 2 (3) :191-196
[23]  
SUGAWARA I, 1988, CANCER RES, V48, P1926
[24]  
Terwillinger JD, 1994, HDB HUMAN GENETIC LI
[25]   Impact of cytochrome P450 3A5 genetic polymorphism on tacrolimus doses and concentration-to-dose ratio in renal transplant recipients [J].
Thervet, E ;
Anglicheau, D ;
King, B ;
Schlageter, MH ;
Cassinat, B ;
Beaune, P ;
Legendre, C ;
Daly, AK .
TRANSPLANTATION, 2003, 76 (08) :1233-1235
[26]   Tacrolimus trough level adjustment after administration of fluconazole to kidney recipients [J].
Toda, F ;
Tanabe, K ;
Ito, S ;
Shinmura, H ;
Tokumoto, T ;
Ishida, H ;
Toma, H .
TRANSPLANTATION PROCEEDINGS, 2002, 34 (05) :1733-1735
[27]   Neurotoxicity induced by tacrolimus after liver transplantation:: Relation to genetic polymorphisms of the ABCB1 (MDR1) gene [J].
Yamauchi, A ;
Ieiri, I ;
Kataoka, Y ;
Tanabe, M ;
Nishizaki, T ;
Oishi, R ;
Higuchi, S ;
Otsubo, K ;
Sugimachi, K .
TRANSPLANTATION, 2002, 74 (04) :571-573