抗がん剤治療時における P-glycoproteinの発現・機能変動と薬物動態並びに薬理作用へ及ぼす影響

抄録

In pharmaceutical therapy, the onset of pharmacological and adverse effects of drugs varies widely among individuals. Since these effects are mostly dependent on the blood level of each drug, it is particularly important to monitor and regulate those levels after drug administration. Factors influencing the pharmacokinetics and pharmacodynamics of drugs include drug transporters, drug metabolizing enzymes and the plasma protein-binding ratio. Among these factors, we focused on P-glycoprotein (P-gp), a drug efflux transporter. The expression and function of P-gp are reported to alter under several pathological conditions and by administrating some foods or substrate drugs for P-gp.
In this mini-review, we introduce alterations in the expression and functional activity of P-gp by anti-cancer drugs, most of which are P-gp substrates, in addition to their mechanism of action. In tumorous or healthy tissues, the expression and function of P-gp were increased by chronic exposure to anti-cancer drugs. A large number of previous studies have proposed that not only various transcriptional factors for P-gp but also post-translational factors such as ezrin/radixin/moesin are involved in changes in P-gp. The expression and function of P-gp seem to be altered during anti-cancer treatment possibly through the above pathways, which may in turn affect the pharmacokinetics and pharmacodynamics of drugs. Therefore, the response should take into account the kinds of drugs each patient uses and their status of P-gp expression and function in clinical pharmacotherapy.