Unmasking the dynamic interplay between efflux transporters and metabolic enzymes

International Journal of Pharmaceutics

Volumn 277, Issue 1-2, 2004, Pages 3-9

  Benet, L Z ^a   Cummins, C L ^a   Wu, C Y ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Caco 2 cells; CYP3A4; Felodipine; Metabolism; Midazolam; P glycoprotein; Sex differences; Sirolimus; Tacrolimus; Transport

Indexed keywords

CYCLOSPORIN; CYSTEINE PROTEINASE INHIBITOR; CYTOCHROME P450 3A4; CYTOCHROME P450 INHIBITOR; DRUG METABOLIZING ENZYME; ELACRIDAR; FELODIPINE; GLYCOPROTEIN P; GLYCOPROTEIN P INHIBITOR; MIDAZOLAM; RAPAMYCIN; TRAMAZOLINE; TROLEANDOMYCIN;

CONCENTRATION (PARAMETERS); CONFERENCE PAPER; DRUG METABOLISM; DRUG TRANSPORT; ENZYME SUBSTRATE; HUMAN; INTESTINE ABSORPTION; LIVER METABOLISM; MOLECULAR DYNAMICS; NONHUMAN; PRIORITY JOURNAL; SEX DIFFERENCE; TRANSPORT KINETICS;

ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; ORGAN SPECIFICITY; P-GLYCOPROTEIN;

EID: 2442719906     PISSN: 03785173     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ijpharm.2002.12.002     Document Type: Conference Paper

References (23)

1. Artursson P., Borchardt R.T. Intestinal drug absorption and metabolism in cell cultures: Caco-2 and beyond. Pharm. Res. 14:1997;1655-1658
2. Benet L.Z., Cummins C.L. The drug efflux-metabolism alliance: biochemical aspects. Adv. Drug Deliv. Rev. 50:2001;S3-S11
3. Benet L.Z., Wu C.-Y., Hebert M.F., Wacher V.J. Intestinal drug metabolism and antitransport processes: a potential paradigm shift in oral drug delivery. J. Control. Release. 39:1996;139-143
4. Cummins C.L., Mangravite L.M., Benet L.Z. Characterizing the expression of CYP3A4 and efflux transporters (P-gp, MRP1, and MRP2) in CYP3A4-transfected Caco-2 cells after induction with sodium butyrate and the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Pharm. Res. 18:2001;1102-1109
5. Cummins C.L., Jacobsen W., Benet L.Z. Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4. J. Pharmacol. Exp. Ther. 300:2002a;1036-1045
6. Cummins C.L., Wu C.-Y., Benet L.Z. Sex differences in the clearance of cytochrome P450 3A4 substrates may be caused by P-glycoprotein. Clin. Pharmacol. Ther. 72:2002b;474-489
7. Cummins C.L., Salphati L., Reid M.J., Benet L.Z. In vivo modulation of intestinal CYP3A metabolism by P-glycoprotein: studies using the rat single-pass intestinal perfusion model. J. Pharmacol. Exp. Ther. 305:2003;306-314
8. 3-modified Caco-2 cell monolayers. J. Pharmacol. Exp. Ther. 289:1999;1134-1142
9. Gutmann H., Fricker G., Török M., Michael S., Beglinger C., Drewe J. Evidence for different ABC-transporters in Caco-2 cells modulating drug uptake. Pharm. Res. 16:1999;402-407
10. Hamilton R.L., Berry M.N., Williams M.C., Severinghaus E.M. A simple and inexpensive membrane "lung" for small organ perfusion. J. Lipid Res. 15:1974;182-186
11. Harris R.Z., Benet L.Z., Schwartz J.B. Gender effects in pharmacokinetics and pharmacodynamics. Drugs. 50:1995;222-239
12. Jacobsen W., Christians U., Benet L.Z. In vitro evaluation of the disposition of a novel cysteine protease inhibitor. Drug Metab. Dispos. 28:2000;1343-1351
13. Kolars J.C., Lown K.S., Schmiedlin-Ren P., Ghosh M., Fang C., Wrighton S.A., Merion R.M., Watkins P.B. CYP3A gene expression in human gut epithelium. Pharmacogenetics. 4:1994;247-259
14. Meibohm B., Beierle I., Derendorf H. How important are gender differences in pharmacokinetics? Clin. Pharmacokinet. 41:2002;329-342
15. Paine M.F., Shen D.D., Kunze K.L., Perkins J.D., Marsh C.L., McVicar J.P., Barr D.M., Gillies B.S., Thummel K.E. First-pass metabolism by the human intestine. Clin. Pharmacol. Ther. 60:1996;14-24
16. Schuetz E.G., Furuya K.N., Schuetz J.D. Interindividual variation in expression of P-glycoprotein in normal human liver and secondary hepatic neoplasms. J. Pharmacol. Exp. Ther. 275:1995;1011-1018
17. Thiebaut F., Tsuruo T., Hamada H., Gottesman M.M., Pastan I., Willingham M.C. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc. Natl. Acad. Sci. U.S.A. 84:1987;7735-7738
18. Wacher V.J., Salphati L., Benet L.Z. Active secretion and enterocytic drug metabolism barriers to drug absorption. Adv. Drug Deliv. Rev. 20:1996;99-112
19. Wacher V.J., Silverman J.A., Zhang Y., Benet L.Z. Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics. J. Pharm. Sci. 87:1998;1322-1330
20. Watkins P.B., Wrighton S.A., Schuetz E.G., Molowa D.T., Guzelian P.S. Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man. J. Clin. Invest. 80:1987;1029-1036
21. Wu, C.-Y., Benet, L.Z., 2003. Disposition of tacrolimus in isolated perfused rat liver: Influence of troleandomycin, cyclosporine, and GG918. Drug Metab. Dispos. 31, 1292-1295.
22. Zhang Y., Benet L.Z. The gut as a barrier to drug absorption. Clin. Pharmacokinet. 40:2001;159-168
23. Zhang Q.Y., Dunbar D., Ostrowska A., Zeisloft S., Yang J., Kaminsky L.S. Characterization of human small intestinal cytochromes P-450. Drug Metab. Dispos. 27:1999;804-809