Tags

Type your tag names separated by a space and hit enter

Impact of cytochrome P450 3A and ATP-binding cassette subfamily B member 1 polymorphisms on tacrolimus dose-adjusted trough concentrations among Korean renal transplant recipients.
Transplant Proc. 2012 Jan; 44(1):109-14.TP

Abstract

BACKGROUND

Tacrolimus is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), encoded by the CYP3A and ATP-binding cassette subfamily B member 1 (ABCB1) genes, respectively. This study was aimed to investigate the impact of CYP3A and ABCB1 polymorphisms on the tacrolimus pharmacokinetics and clinical outcomes in Korean renal transplant recipients.

METHODS

We analyzed data from a cohort of 70 renal transplant recipients receiving tacrolimus. CYP3A4*4, CYP3A4*5, CYP3A4*18, CYP3A5*3, ABCB1 C1236>T, ABCB1 G2677>T/A, and ABCB1 C3435>T polymorphisms were genotyped and correlated to dose-adjusted tacrolimus trough concentration at months 1, 3, 6, and 12 after transplantation.

RESULTS

Patients with the CYP3A5*3 alleles showed higher dose-adjusted tacrolimus concentrations for 12 months and higher trough levels until 6 months after transplantation. ABCB1 polymorphisms and haplotypes were not associated with tacrolimus concentrations. In a multivariate analysis, the presence of ≥1 CYP3A5*3 allele was a significant independent variable affecting dose-adjusted tacrolimus concentrations. Glomerular filtration rate, acute rejection, opportunistic infection, and graft survival were not affected by CYP3A5 polymorphisms. Calcineurin inhibitor toxicity, which showed higher tendency in patients with CYP3A5*1 alleles, might be associated with higher tacrolimus dose per kilogram.

CONCLUSIONS

The CYP3A5 genotype is a major factor in determining the dose requirement of tacrolimus, and genotyping may be of value in individualization of immunosuppressive therapy of renal transplant patients.

Authors+Show Affiliations

Department of Internal Medicine, Kyungpook National University School of Medicine, Clinical Research Center for End Stage Renal Disease, Daegu, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22310591

Citation

Cho, J-H, et al. "Impact of Cytochrome P450 3A and ATP-binding Cassette Subfamily B Member 1 Polymorphisms On Tacrolimus Dose-adjusted Trough Concentrations Among Korean Renal Transplant Recipients." Transplantation Proceedings, vol. 44, no. 1, 2012, pp. 109-14.
Cho JH, Yoon YD, Park JY, et al. Impact of cytochrome P450 3A and ATP-binding cassette subfamily B member 1 polymorphisms on tacrolimus dose-adjusted trough concentrations among Korean renal transplant recipients. Transplant Proc. 2012;44(1):109-14.
Cho, J. H., Yoon, Y. D., Park, J. Y., Song, E. J., Choi, J. Y., Yoon, S. H., Park, S. H., Kim, Y. L., & Kim, C. D. (2012). Impact of cytochrome P450 3A and ATP-binding cassette subfamily B member 1 polymorphisms on tacrolimus dose-adjusted trough concentrations among Korean renal transplant recipients. Transplantation Proceedings, 44(1), 109-14. https://doi.org/10.1016/j.transproceed.2011.11.004
Cho JH, et al. Impact of Cytochrome P450 3A and ATP-binding Cassette Subfamily B Member 1 Polymorphisms On Tacrolimus Dose-adjusted Trough Concentrations Among Korean Renal Transplant Recipients. Transplant Proc. 2012;44(1):109-14. PubMed PMID: 22310591.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of cytochrome P450 3A and ATP-binding cassette subfamily B member 1 polymorphisms on tacrolimus dose-adjusted trough concentrations among Korean renal transplant recipients. AU - Cho,J-H, AU - Yoon,Y-D, AU - Park,J-Y, AU - Song,E-J, AU - Choi,J-Y, AU - Yoon,S-H, AU - Park,S-H, AU - Kim,Y-L, AU - Kim,C-D, PY - 2012/2/8/entrez PY - 2012/2/9/pubmed PY - 2012/5/25/medline SP - 109 EP - 14 JF - Transplantation proceedings JO - Transplant Proc VL - 44 IS - 1 N2 - BACKGROUND: Tacrolimus is a substrate of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), encoded by the CYP3A and ATP-binding cassette subfamily B member 1 (ABCB1) genes, respectively. This study was aimed to investigate the impact of CYP3A and ABCB1 polymorphisms on the tacrolimus pharmacokinetics and clinical outcomes in Korean renal transplant recipients. METHODS: We analyzed data from a cohort of 70 renal transplant recipients receiving tacrolimus. CYP3A4*4, CYP3A4*5, CYP3A4*18, CYP3A5*3, ABCB1 C1236>T, ABCB1 G2677>T/A, and ABCB1 C3435>T polymorphisms were genotyped and correlated to dose-adjusted tacrolimus trough concentration at months 1, 3, 6, and 12 after transplantation. RESULTS: Patients with the CYP3A5*3 alleles showed higher dose-adjusted tacrolimus concentrations for 12 months and higher trough levels until 6 months after transplantation. ABCB1 polymorphisms and haplotypes were not associated with tacrolimus concentrations. In a multivariate analysis, the presence of ≥1 CYP3A5*3 allele was a significant independent variable affecting dose-adjusted tacrolimus concentrations. Glomerular filtration rate, acute rejection, opportunistic infection, and graft survival were not affected by CYP3A5 polymorphisms. Calcineurin inhibitor toxicity, which showed higher tendency in patients with CYP3A5*1 alleles, might be associated with higher tacrolimus dose per kilogram. CONCLUSIONS: The CYP3A5 genotype is a major factor in determining the dose requirement of tacrolimus, and genotyping may be of value in individualization of immunosuppressive therapy of renal transplant patients. SN - 1873-2623 UR - https://www.unboundmedicine.com/medline/citation/22310591/Impact_of_cytochrome_P450_3A_and_ATP_binding_cassette_subfamily_B_member_1_polymorphisms_on_tacrolimus_dose_adjusted_trough_concentrations_among_Korean_renal_transplant_recipients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-1345(11)01549-1 DB - PRIME DP - Unbound Medicine ER -