Tags

Type your tag names separated by a space and hit enter

Influence of CYP3A5 and MDR1 polymorphisms on tacrolimus concentration in the early stage after renal transplantation.
Clin Transplant. 2005 Oct; 19(5):638-43.CT

Abstract

OBJECTIVE

Tacrolimus is an immunosuppressive drug with a narrow therapeutic range and wide interindividual variation in its pharmacokinetics. Cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp, encoded by MDR1) play an important role in the absorption and metabolism of tacrolimus. The objective of this study was to evaluate whether or not CYP3A5*1/*3 or MDR1 C3435T polymorphisms are associated with the tacrolimus concentration per dose.

METHODS

CYP3A5 and MDR1 genotypes were determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis in 118 Chinese renal transplant patients receiving tacrolimus. Whole blood trough tacrolimus concentration was measured by enzyme-linked immunosorbent assay and dose-adjusted concentration (ng/mL per mg/kg/d) was calculated at 1 wk, 1 month, and 3 months after transplantation.

RESULTS

The dose-adjusted concentration of CYP3A5*1/*1 and *1/*3 patients was significantly lower than *3/*3 patients (32.8 +/- 17.7 and 41.6 +/- 15.8 vs. 102.3 +/- 51.2 at 1 wk; 33.1 +/- 7.5 and 46.4 +/- 12.9 vs. 103 +/- 47.5 at 1 month; 35.3 +/- 20.9 and 59.0 +/- 20.6 vs. 150 +/- 85.3 at 3 months after transplantation respectively). At 1 wk, 46% of the CYP3A5*1 allele carriers had a tacrolimus concentration lower than 5 ng/mL and 77% lower than 8 ng/mL, whereas 20% of the *3/*3 patients had a concentration higher than 20 ng/mL. There was a mild difference between *1/*1 homozygotes and *1/*3 heterozygotes at 1 and 3 months after transplantation. No difference was found among the MDR1 genotypes.

CONCLUSION

CYP3A5*1/*3 polymorphisms are associated with tacrolimus pharmacokinetics and dose requirements in renal transplant recipients. Pharmacogenetic methods could be employed prospectively to help initial dose selection and to individualize immunosuppressive therapy.

Authors+Show Affiliations

Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

16146556

Citation

Zhang, Xin, et al. "Influence of CYP3A5 and MDR1 Polymorphisms On Tacrolimus Concentration in the Early Stage After Renal Transplantation." Clinical Transplantation, vol. 19, no. 5, 2005, pp. 638-43.
Zhang X, Liu ZH, Zheng JM, et al. Influence of CYP3A5 and MDR1 polymorphisms on tacrolimus concentration in the early stage after renal transplantation. Clin Transplant. 2005;19(5):638-43.
Zhang, X., Liu, Z. H., Zheng, J. M., Chen, Z. H., Tang, Z., Chen, J. S., & Li, L. S. (2005). Influence of CYP3A5 and MDR1 polymorphisms on tacrolimus concentration in the early stage after renal transplantation. Clinical Transplantation, 19(5), 638-43.
Zhang X, et al. Influence of CYP3A5 and MDR1 Polymorphisms On Tacrolimus Concentration in the Early Stage After Renal Transplantation. Clin Transplant. 2005;19(5):638-43. PubMed PMID: 16146556.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of CYP3A5 and MDR1 polymorphisms on tacrolimus concentration in the early stage after renal transplantation. AU - Zhang,Xin, AU - Liu,Zhi-hong, AU - Zheng,Jing-min, AU - Chen,Zhao-hong, AU - Tang,Zheng, AU - Chen,Jin-song, AU - Li,Lei-shi, PY - 2005/9/9/pubmed PY - 2005/12/15/medline PY - 2005/9/9/entrez SP - 638 EP - 43 JF - Clinical transplantation JO - Clin Transplant VL - 19 IS - 5 N2 - OBJECTIVE: Tacrolimus is an immunosuppressive drug with a narrow therapeutic range and wide interindividual variation in its pharmacokinetics. Cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp, encoded by MDR1) play an important role in the absorption and metabolism of tacrolimus. The objective of this study was to evaluate whether or not CYP3A5*1/*3 or MDR1 C3435T polymorphisms are associated with the tacrolimus concentration per dose. METHODS: CYP3A5 and MDR1 genotypes were determined by polymerase chain reaction followed by restriction fragment length polymorphism analysis in 118 Chinese renal transplant patients receiving tacrolimus. Whole blood trough tacrolimus concentration was measured by enzyme-linked immunosorbent assay and dose-adjusted concentration (ng/mL per mg/kg/d) was calculated at 1 wk, 1 month, and 3 months after transplantation. RESULTS: The dose-adjusted concentration of CYP3A5*1/*1 and *1/*3 patients was significantly lower than *3/*3 patients (32.8 +/- 17.7 and 41.6 +/- 15.8 vs. 102.3 +/- 51.2 at 1 wk; 33.1 +/- 7.5 and 46.4 +/- 12.9 vs. 103 +/- 47.5 at 1 month; 35.3 +/- 20.9 and 59.0 +/- 20.6 vs. 150 +/- 85.3 at 3 months after transplantation respectively). At 1 wk, 46% of the CYP3A5*1 allele carriers had a tacrolimus concentration lower than 5 ng/mL and 77% lower than 8 ng/mL, whereas 20% of the *3/*3 patients had a concentration higher than 20 ng/mL. There was a mild difference between *1/*1 homozygotes and *1/*3 heterozygotes at 1 and 3 months after transplantation. No difference was found among the MDR1 genotypes. CONCLUSION: CYP3A5*1/*3 polymorphisms are associated with tacrolimus pharmacokinetics and dose requirements in renal transplant recipients. Pharmacogenetic methods could be employed prospectively to help initial dose selection and to individualize immunosuppressive therapy. SN - 0902-0063 UR - https://www.unboundmedicine.com/medline/citation/16146556/Influence_of_CYP3A5_and_MDR1_polymorphisms_on_tacrolimus_concentration_in_the_early_stage_after_renal_transplantation_ L2 - https://doi.org/10.1111/j.1399-0012.2005.00370.x DB - PRIME DP - Unbound Medicine ER -