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Impact of CYP3A5 and MDR1(ABCB1) C3435T polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients.
Transplant Proc. 2005 May; 37(4):1730-2.TP

Abstract

OBJECTIVE

The objective of this study was to assess the influence of CYP3A5 and MDR1 genetic polymorphisms on tacrolimus pharmacokinetics in Japanese renal transplant recipients.

METHOD

The pharmacokinetic parameters of tacrolimus were calculated in steady-state on day 28 after transplantation. Polymerase chain reaction-restriction fragment length polymorphism and direct sequence methods were used for CYP3A5 and MDR1 polymorphisms, respectively.

RESULTS

The dose-adjusted area under the concentration-time curve (AUC0-12) was significantly lower among CYP3A5*1 carriers than those bearing CYP3A5*3/*3. (0.570 +/- 0.105 vs 0.865 +/- 0.343 ng.h/mL per mg/kg, P = .00322). The daily tacrolimus dose per body weight was significantly higher in CYP3A5*1 carriers than those of CYP3A5*3/*3 carriers (0.271 +/- 0.110 vs 0.150 +/- 0.056 mg/kg, P = .00016). In this study, a distinction was made between carriers of CYP3A5*1/*1+*1/*3 and CYP3A5*3/*3 to investigate the influence of the MDR1 C3435T mutation on tacrolimus pharmacokinetics. The MDR1 C3435T polymorphisms did not affect any tacrolimus pharmacokinetic parameter in either group.

CONCLUSIONS

Renal transplant recipients who were CYP3A5*1 carriers required a higher dose of tacrolimus than CYP3A5*3/*3, indicating a significantly lower dose-adjusted AUC0-12 of tacrolimus. In contrast, MDR1 C3435T polymorphism was not an important factor in tacrolimus pharmacokinetics.

Authors+Show Affiliations

Department of Pharmaceutical Science, Akita University School of Medicine, Hondo, Akita, Japan.No affiliation info availableNo 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

15919447

Citation

Tada, H, et al. "Impact of CYP3A5 and MDR1(ABCB1) C3435T Polymorphisms On the Pharmacokinetics of Tacrolimus in Renal Transplant Recipients." Transplantation Proceedings, vol. 37, no. 4, 2005, pp. 1730-2.
Tada H, Tsuchiya N, Satoh S, et al. Impact of CYP3A5 and MDR1(ABCB1) C3435T polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients. Transplant Proc. 2005;37(4):1730-2.
Tada, H., Tsuchiya, N., Satoh, S., Kagaya, H., Li, Z., Sato, K., Miura, M., Suzuki, T., Kato, T., & Habuchi, T. (2005). Impact of CYP3A5 and MDR1(ABCB1) C3435T polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients. Transplantation Proceedings, 37(4), 1730-2.
Tada H, et al. Impact of CYP3A5 and MDR1(ABCB1) C3435T Polymorphisms On the Pharmacokinetics of Tacrolimus in Renal Transplant Recipients. Transplant Proc. 2005;37(4):1730-2. PubMed PMID: 15919447.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impact of CYP3A5 and MDR1(ABCB1) C3435T polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients. AU - Tada,H, AU - Tsuchiya,N, AU - Satoh,S, AU - Kagaya,H, AU - Li,Z, AU - Sato,K, AU - Miura,M, AU - Suzuki,T, AU - Kato,T, AU - Habuchi,T, PY - 2005/5/28/pubmed PY - 2005/9/24/medline PY - 2005/5/28/entrez SP - 1730 EP - 2 JF - Transplantation proceedings JO - Transplant Proc VL - 37 IS - 4 N2 - OBJECTIVE: The objective of this study was to assess the influence of CYP3A5 and MDR1 genetic polymorphisms on tacrolimus pharmacokinetics in Japanese renal transplant recipients. METHOD: The pharmacokinetic parameters of tacrolimus were calculated in steady-state on day 28 after transplantation. Polymerase chain reaction-restriction fragment length polymorphism and direct sequence methods were used for CYP3A5 and MDR1 polymorphisms, respectively. RESULTS: The dose-adjusted area under the concentration-time curve (AUC0-12) was significantly lower among CYP3A5*1 carriers than those bearing CYP3A5*3/*3. (0.570 +/- 0.105 vs 0.865 +/- 0.343 ng.h/mL per mg/kg, P = .00322). The daily tacrolimus dose per body weight was significantly higher in CYP3A5*1 carriers than those of CYP3A5*3/*3 carriers (0.271 +/- 0.110 vs 0.150 +/- 0.056 mg/kg, P = .00016). In this study, a distinction was made between carriers of CYP3A5*1/*1+*1/*3 and CYP3A5*3/*3 to investigate the influence of the MDR1 C3435T mutation on tacrolimus pharmacokinetics. The MDR1 C3435T polymorphisms did not affect any tacrolimus pharmacokinetic parameter in either group. CONCLUSIONS: Renal transplant recipients who were CYP3A5*1 carriers required a higher dose of tacrolimus than CYP3A5*3/*3, indicating a significantly lower dose-adjusted AUC0-12 of tacrolimus. In contrast, MDR1 C3435T polymorphism was not an important factor in tacrolimus pharmacokinetics. SN - 0041-1345 UR - https://www.unboundmedicine.com/medline/citation/15919447/Impact_of_CYP3A5_and_MDR1_ABCB1__C3435T_polymorphisms_on_the_pharmacokinetics_of_tacrolimus_in_renal_transplant_recipients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-1345(05)00190-9 DB - PRIME DP - Unbound Medicine ER -