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Role of BCRP 421C>A polymorphism on rosuvastatin pharmacokinetics in healthy Chinese males.
Clin Chim Acta. 2006 Nov; 373(1-2):99-103.CC

Abstract

BACKGROUND

Rosuvastatin, a novel potent HMG-CoA reductase inhibitor, is excreted into bile mediated by breast cancer resistance protein (BCRP). Our objective was to determine the association between the most frequent single nucleotide polymorphisms (SNPs) of the BCRP (421C>A) and the pharmacokinetics of rosuvastatin.

METHOD

Pre-screening of SLCO1B1 521TC and CYP2C9*1/*3 were performed before this pharmacokinetic study. Fourteen healthy volunteers who are SLCO1B1 521TT and CYP2C9*1/*1 wild-type homozygotes were selected to participate in this study. Seven were 421CC wild-type of BCRP, the others were carriers with at least one 421C>A mutant allele (five subjects had a genotype of 421CA and two were homozygotes of 421AA). Each was given a single oral dose of 20 mg rosuvastatin. The plasma concentrations of rosuvastatin were measured for up to 72 h by LC-MS.

RESULTS

The pharmacokinetic parameters of rosuvastatin showed a significantly difference between the two genotyped groups. The AUC(0-72) and AUC(0-infinity) of rosuvastatin were lower in the 421CC group than in the 421CA+421AA group (33.8+/-11.4 vs. 59.6+/-22.2 ng.h/ml, P=0.018; 34.9+/-11.9 vs. 62.2+/-23.5 ng.h/ml, P=0.018), respectively. The C(max) value was higher in the 421CA+421AA group than that in the 421CC group (9.9+/-5.4 vs. 5.1+/-2.4 ng/ml, P=0.048). The CL/F value was lower in the 421CA+421AA group than that in the 421CC group (384.7+/-161.2 vs. 674.0+/-297.6 l/h, P=0.043). The T(1/2) and T(max) values showed no difference between these groups.

CONCLUSIONS

The BCRP 421C>A polymorphism may play an important role in the pharmacokinetics of rosuvastatin in healthy Chinese males after the exclusion of impact of SLCO1B1 and CYP2C9 genetic polymorphism.

Authors+Show Affiliations

Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan 410078, P.R. China.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 availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16784736

Citation

Zhang, Wei, et al. "Role of BCRP 421C>A Polymorphism On Rosuvastatin Pharmacokinetics in Healthy Chinese Males." Clinica Chimica Acta; International Journal of Clinical Chemistry, vol. 373, no. 1-2, 2006, pp. 99-103.
Zhang W, Yu BN, He YJ, et al. Role of BCRP 421C>A polymorphism on rosuvastatin pharmacokinetics in healthy Chinese males. Clin Chim Acta. 2006;373(1-2):99-103.
Zhang, W., Yu, B. N., He, Y. J., Fan, L., Li, Q., Liu, Z. Q., Wang, A., Liu, Y. L., Tan, Z. R., Fen-Jiang, ., Huang, Y. F., & Zhou, H. H. (2006). Role of BCRP 421C>A polymorphism on rosuvastatin pharmacokinetics in healthy Chinese males. Clinica Chimica Acta; International Journal of Clinical Chemistry, 373(1-2), 99-103.
Zhang W, et al. Role of BCRP 421C>A Polymorphism On Rosuvastatin Pharmacokinetics in Healthy Chinese Males. Clin Chim Acta. 2006;373(1-2):99-103. PubMed PMID: 16784736.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of BCRP 421C>A polymorphism on rosuvastatin pharmacokinetics in healthy Chinese males. AU - Zhang,Wei, AU - Yu,Bang-Ning, AU - He,Yi-Jing, AU - Fan,Lan, AU - Li,Qing, AU - Liu,Zhao-Qian, AU - Wang,An, AU - Liu,Ya-Li, AU - Tan,Zhi-Rong, AU - Fen-Jiang,, AU - Huang,Yuan-Fei, AU - Zhou,Hong-Hao, Y1 - 2006/05/13/ PY - 2006/02/23/received PY - 2006/05/07/revised PY - 2006/05/08/accepted PY - 2006/6/21/pubmed PY - 2006/12/23/medline PY - 2006/6/21/entrez SP - 99 EP - 103 JF - Clinica chimica acta; international journal of clinical chemistry JO - Clin. Chim. Acta VL - 373 IS - 1-2 N2 - BACKGROUND: Rosuvastatin, a novel potent HMG-CoA reductase inhibitor, is excreted into bile mediated by breast cancer resistance protein (BCRP). Our objective was to determine the association between the most frequent single nucleotide polymorphisms (SNPs) of the BCRP (421C>A) and the pharmacokinetics of rosuvastatin. METHOD: Pre-screening of SLCO1B1 521TC and CYP2C9*1/*3 were performed before this pharmacokinetic study. Fourteen healthy volunteers who are SLCO1B1 521TT and CYP2C9*1/*1 wild-type homozygotes were selected to participate in this study. Seven were 421CC wild-type of BCRP, the others were carriers with at least one 421C>A mutant allele (five subjects had a genotype of 421CA and two were homozygotes of 421AA). Each was given a single oral dose of 20 mg rosuvastatin. The plasma concentrations of rosuvastatin were measured for up to 72 h by LC-MS. RESULTS: The pharmacokinetic parameters of rosuvastatin showed a significantly difference between the two genotyped groups. The AUC(0-72) and AUC(0-infinity) of rosuvastatin were lower in the 421CC group than in the 421CA+421AA group (33.8+/-11.4 vs. 59.6+/-22.2 ng.h/ml, P=0.018; 34.9+/-11.9 vs. 62.2+/-23.5 ng.h/ml, P=0.018), respectively. The C(max) value was higher in the 421CA+421AA group than that in the 421CC group (9.9+/-5.4 vs. 5.1+/-2.4 ng/ml, P=0.048). The CL/F value was lower in the 421CA+421AA group than that in the 421CC group (384.7+/-161.2 vs. 674.0+/-297.6 l/h, P=0.043). The T(1/2) and T(max) values showed no difference between these groups. CONCLUSIONS: The BCRP 421C>A polymorphism may play an important role in the pharmacokinetics of rosuvastatin in healthy Chinese males after the exclusion of impact of SLCO1B1 and CYP2C9 genetic polymorphism. SN - 0009-8981 UR - https://www.unboundmedicine.com/medline/citation/16784736/Role_of_BCRP_421C>A_polymorphism_on_rosuvastatin_pharmacokinetics_in_healthy_Chinese_males_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-8981(06)00266-X DB - PRIME DP - Unbound Medicine ER -