1、2370 31 23 2015 12 205 Application of physiological based pharmacokinetic model in transport mediated drugdrug interactions 2015 09 26 2015 11 09 1990 MP 18611513192E mail 1 Clinical Pharmacology esearch Center Peking Union Medical CollegeHospital Peking Union Medical Co-llege and Chinese Academy of
2、 MedicalSciences Beijing 100032 China 2 Pharmaceutical College of Zhengzhou University Zhengzhou 450001 China DDIs。PBPK DDIs。PBPK PBPK DDIs。DOI 10.13699/ki.1001 6821.2015.23.030 969.1 969.2 A 1001 6821 2015 23 2370 03Abstract With the deepening of understanding on transporters trans-porter mediated
3、drug drug interactions DDIs have become a focus bothin drug development and clinical practice.CYP mediated static modelhas played a important role in the prediction of DDIs for a long time.e-cently the simulation and prediction based physiologically based pharma-cokinetic PBPK model is gradually bec
4、oming the new direction for theDDIs research.In this paper we make a compare about the static modeland PBPK model which focus on the application of PBPK model intransporter mediated DDIs and hope to provide some reference for therelated research in the future.Key words transport drug drug interactio
5、n dynamic model staticmodel、。DDIs 1 2。DDIs PBPK。DDIs。PBPK FDA PBPK。PBPK DDIs。1 DDIs、DDIs Chin J Clin Pharmacol 2371Vol.31 No.23 December 2015 Serial No.205 DDIs。DDIs DDIs。Endres 3 f u I Ki AUC=AUCinhibition/AUC=1+f u I/Ki DDIs。FDA DDIs 7 P P gp、BCP、1B1 OATP1B1、1B3 OATP1B3、2 OCT2、1 OAT1、3 OAT3 2。f u
6、I/Ki 0.1 DDIs。OATPs OATPs AUC 2 20 4 5。DDIs Cmax Cmax f u 6。DDIs。DDIs。Yoshida 7 58 DDIs AUCs 2 3、。DDIs DDIs。PBPK。2 PBPK DDIs PBPK。2008 2013 FDA DDIs 84 PBPK DDIs。PBPK“”。10 PBPK DDIs SimCYP DDIs FDA、EMA。2.1 PBPK DDIs PBPK DDIs。Fenneteau 8 PBPK P gp/P gp PBPK P gp、P gp DDIs。Jones 9 PBPK 7 OATP IVIVE P
7、BPK OATP。Watanabe 10 IVIVE PBPK OATP1B1 MP2。Varma 11 PBPK OATP1B1、DDIs DDIs。PBPK DDIs。DDIs DDIs PBPK、12 PBPK、13。2.2 PBPK DDIs DDIs 14。PBPK DDIs。2372 31 23 2015 12 205、DDIs。Gertz 5 PBPK AM1 OATPs、NTCP、P gp、MP2、BSEP BCP PBPK DDIs。OATP1B1 70%。50 P gp CYP3A4 80%97%。DDI PBPK DDIs PBPK DDIs。3 DDIs DDIs。、。
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