Impact of genetic polymorphisms in transmembrane carrier-systems on drug and xenobiotic distribution

被引:44
作者
Gerloff, T [1 ]
机构
[1] Humboldt Univ, Charite Univ Med Ctr, Inst Clin Pharmacol, D-10098 Berlin, Germany
关键词
pharmacogenetics; transmembrane transporters; drug disposition; polymorphisms; blood tissue barriers; uptake; efflux;
D O I
10.1007/s00210-003-0813-5
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Active transport across biological membranes has become a noticeable factor in the absorption, distribution, and excretion of an increasing number of drugs. Different transmembrane transport systems including organic anion transporters (OATP, solute carrier family SLC21A), organic cation transporters (OCT, SLC22A), dipeptide transporters (PEPT, SLC15A), nucleoside transporters (CNT, SLC28A), monocarboxylate carriers (MCT, SLC2A), and members of the large ATP-binding cassette family (ABC, SLC3A) are involved in drug disposition. Genetic polymorphisms in transport proteins frequently occur and contribute to interindividual differences in the efficacy and safety of pharmatherapy. Currently, the most advanced research has been done on P-glycoprotein (ABCB1, SLC3A1.201.1). Knowledge of this transporter indicates that haplotype analysis rather than association with single nucleotide polymorphisms (SNPs) provides the most appropriate interpretation of pharmacogenetic data from drug transporters. This review gives an overview and update on the pharmacological impact of genetic variants in transmembrane transporters.
引用
收藏
页码:69 / 77
页数:9
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