CYP3A5 Genotype Is Not Related to the Intrapatient Variability of Tacrolimus Clearance

被引：30

作者：

Pashaee, Nilufar ^{[1
]}

Bouamar, Rachida ^{[1
]}

Hesselink, Dennis A. ^{[2
]}

Roodnat, Joke I. ^{[2
]}

van Schaik, Ron H. N. ^{[3
]}

Weimar, Willem ^{[2
]}

van Gelder, Teun ^{[1
,2
]}

机构：

[1] Erasmus MC, Dept Hosp Pharm, Clin Pharmacol Unit, NL-3000 CA Rotterdam, Netherlands

[2] Erasmus MC, Dept Internal Med, Div Nephrol & Renal Transplantat, NL-3000 CA Rotterdam, Netherlands

[3] Erasmus MC, Dept Clin Chem, NL-3000 CA Rotterdam, Netherlands

来源：

THERAPEUTIC DRUG MONITORING | 2011年 / 33卷 / 03期

关键词：

CYP3A5; kidney transplantation; intrapatient variability; tacrolimus; pharmacogenetics; RENAL-TRANSPLANT RECIPIENTS; DRUG-INTERACTIONS; POLYMORPHISMS; RISK;

D O I：

10.1097/FTD.0b013e31821a7aa3

中图分类号：

R446 [实验室诊断]; R-33 [实验医学、医学实验];

学科分类号：

1001 ;

摘要：

Background: The risk of long-term chronic allograft nephropathy and graft loss after kidney transplantation is increased in patients with a high intrapatient variability of tacrolimus (Tac) clearance. Methods: To test whether this intrapatient variability is associated with an individual's CYP3A5 genotype, we measured the intrapatient variability in Tac clearance in a cohort of 208 kidney transplant recipients treated with Tac and mycophenolate mofetil. Results: Tac dose requirement was significantly higher in patients expressing CYP3A5. However, intraindividual variability of Tac clearance was not related to CYP3A5 genotype. Conclusions: Intraindividual variability in Tac clearance is not related to CYP3A5 genotype. Other factors, including patient adherence, may explain the variability in Tac clearance within an individual patient over time.

引用

页码：369 / 371

页数：3

共 16 条

[1] Cytochrome P450 3A polymorphisms and immunosuppressive drugs:: an update [J].

Anglicheau, Dany ;

Legendre, Christophe ;

Beaune, Philippe ;

Thervet, Eric .

PHARMACOGENOMICS, 2007, 8 (07) :835-849

[2] High within-patient variability in the clearance of tacrolimus is a risk factor for poor long-term outcome after kidney transplantation [J].

Borra, Lennaert C. P. ;

Roodnat, Joke I. ;

Kal, Judith A. ;

Mathot, Ron A. A. ;

Weimar, Willem ;

van Gelder, Teun .

NEPHROLOGY DIALYSIS TRANSPLANTATION, 2010, 25 (08) :2757-2763

[3] CYP3A5*1/*3 genotype influences the blood concentration of tacrolimus in response to metabolic inhibition by ketoconazole [J].

Chandel, Nirupama ;

Aggarwal, Pardeep K. ;

Minz, Mukut ;

Sakhuja, Vinay ;

Kohli, Krishan K. ;

Jha, Vivekanand .

PHARMACOGENETICS AND GENOMICS, 2009, 19 (06) :458-463

[4] CYP3A5*3 Genotype Associated With Intrasubject Pharmacokinetic Variation Toward Tacrolimus in Bioequivalence Study [J].

Chung, Jae Yong ;

Lee, Yoon Jung ;

Jang, Seong Bok ;

Lim, Lay Ahyoung ;

Park, Min Soo ;

Kim, Kyung Hwan .

THERAPEUTIC DRUG MONITORING, 2010, 32 (01) :67-72

[5] Genotype-phenotype associations for common CYP3A4 and CYP3A5 variants in the basal and induced metabolism of midazolam in European- and African-American men and women [J].

Floyd, MD ;

Gervasini, G ;

Masica, AL ;

Mayo, G ;

George, AL ;

Bhat, K ;

Kim, RB ;

Wilkinson, GR .

PHARMACOGENETICS, 2003, 13 (10) :595-606

[6] Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus [J].

Hesselink, DA ;

van Schaik, RHN ;

van der Heiden, IP ;

van der Werf, M ;

Gregoor, PJHS ;

Lindemans, J ;

Weimar, W ;

van Gelder, T .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 2003, 74 (03) :245-254

[7] CYP3A5 genotype is not associated with a higher risk of acute rejection in tacrolimus-treated renal transplant recipients [J].

Hesselink, Dennis A. ;

van Schaik, Ron H. N. ;

van Agteren, Madelon ;

de Fijter, Johannes W. ;

Hartmann, Anders ;

Zeier, Martin ;

Budde, Klemens ;

Kuypers, Dirk R. J. ;

Pisarski, Przemyslav ;

Le Meur, Yann ;

Mamelok, Richard D. ;

van Gelder, Teun .

PHARMACOGENETICS AND GENOMICS, 2008, 18 (04) :339-348

[8] Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression [J].

Kuehl, P ;

Zhang, J ;

Lin, Y ;

Lamba, J ;

Assem, M ;

Schuetz, J ;

Watkins, PB ;

Daly, A ;

Wrighton, SA ;

Hall, SD ;

Maurel, P ;

Relling, M ;

Brimer, C ;

Yasuda, K ;

Venkataramanan, R ;

Strom, S ;

Thummel, K ;

Boguski, MS ;

Schuetz, E .

NATURE GENETICS, 2001, 27 (04) :383-391

[9] Effects of CYP3A5 and MDR1 single nucleotide polymorphisms on drug interactions between tacrolimus and fluconazole in renal allograft recipients [J].

Kuypers, Dirk R. ;

de Jonge, Hylke ;

Naesens, Maarten ;

Vanrenterghem, Yves .

PHARMACOGENETICS AND GENOMICS, 2008, 18 (10) :861-868

[10] Black renal transplant recipients have poorer long-term graft survival than CYP3A5 expressers from other ethnic groups [J].

Ng, Fu Liang ;

Holt, David W. ;

Chang, Rene W. S. ;

MacPhee, Iain A. M. .

NEPHROLOGY DIALYSIS TRANSPLANTATION, 2010, 25 (02) :628-634

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