[Application of real-time PCR to pharmacokinetic studies].
Pharmacokinetics is a discipline dealing with processes describing the fate of a drug in the body, starting from its absorption at the site of administration, through its distribution to tissues, metabolism via enzymes, mainly those of the cytochrome P450 family, and to its elimination from the body. In both drug absorption and distribution processes, membrane transporters are often involved, among which P-glycoprotein and organic anion transporting polypeptides (OATP) are probably the best known. Genes coding these proteins as well as many drug metabolizing enzymes are not only highly polymorphic, but their expression may also be significantly altered by the administered drugs. Real-time polymerase chain reaction (real-time PCR) is a sensitive and reliable technique enabling quantitative determination of mRNA levels in cells and tissues. It may also be used for rapid genotyping, and is thus especially useful in a clinical setting as well as for validating microarray data.The aim of this review is to present the utility of real-time PCR in pharmacokinetic studies with special attention paid to the analysis of the expressions of genes coding drug-metabolizing enzymes and membrane transporters as well as to recent studies concerning the impact of genotype on drug pharmacokinetics. Moreover, possibilities of applying this method to collect data for pharmacokinetic and pharmacokinetic-pharmacodynamic modeling (PK/PD) are indicated.
Wyska
Elzbieta
E
Zakład Farmakokinetyki i Farmacji Fizycznej, Wydział Farmaceutyczny, Collegium Medicum, Uniwersytet Jagielloński w Krakowie. mfwyska@cyf-kr.edu.pl
Rosiak
Mateusz
M
D000465:Algorithms; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006801:Humans; D053858:Metabolic Networks and Pathways; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010599:Pharmacokinetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism
D004364:Pharmaceutical Preparations; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System