Potential Role of P-Glycoprotein in Affecting Hepatic Metabolism of Drugs

R. B. Kim, C. Wandel, B. Leake, M. Cvetkovic, M. F. Fromm, P. J. Dempsey, M. M. Roden, F. Belas, A. K. Chaudhary, D. M. Roden, A. J. Wood, and G. R. Wilkinson. Interrelationship between substrates and inhibitors of human CYP3A and P-glycoprotein. Pharm. Res. 16:408–414 (1999). E. G. Schuetz and A. H. Schinkel. Drug disposition as determined by the interplay between drug-transporting and drug-metabolizing systems. J. Biochem. Mol. Toxicol. 13:219–22 (1999). K. Yokogawa, M. Takahashi, I. Tamai, H. Konishi, M. Nomura, S. Moritani, K. Miyamoto, and A. Tsuji. P-glycoprotein-dependent disposition kinetics of tacrolimus: Studies in mdr1a knockout mice. Pharm. Res. 16:1213–1218 (1999). L. Z. Benet, C. Y. Wu, M. F. Hebert, and V. J. Wacher. Intestinal drug metabolism and antitransport processes: A potential paradigm shift in oral drug delivery. J. Controlled Rel. 39:139–143 (1996). E. G. Schuetz, A. H. Schinkel, M. V. Relling, and J. D. Schuetz. P-glycoprotein: A major determinant of rifampicin-inducible expression of cytochrome P4503A in mice and humans. Proc. Natl. Acad. Sci. U.S.A. 93:4001–4005 (1996). E. G. Schuetz, D. R. Umbenhauer, K. Yasuda, C. Brimer, L. Nguyen, M. V. Relling, J. D. Schuetz, and A. H. Schinkel. Altered expression of hepatic cytochromes P-450 in mice deficient in one or more mdr1 genes. Mol. Pharmacol. 57:188–197 (2000). W. L. Chiou, S. M. Chung, and T. C. Wu. Apparent lack of effect of P-glycoprotein on the gastrointestinal absorption of a substrate, tacrolimus, in normal mice. Pharm. Res. 17:205–208 (2000). J. van Asperen, A. H. Schinkel. J. H. Beijen, W. J. Nooijen, P. Borst, and O. van Tellingen. Altered pharmacokinetics of vinblastine in mdr1a P-glycoprotein-deficient mice. J. Natl. Cancer Inst. 88:994–999 (1996). A. Sparreboom, J. van Asperen, U. Mayer, A. H. Schinkel, J. W. Smit, D. K. Meijer, P. Borst, W. J. Nooijen, J. H. Beijnen, and O. van Tellingen. Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc. Natl. Acad. Sci. U.S.A. 94:2031–2035 (1997). E. G. Schuetz, K. Yasuda, K. Arimori, and J. D. Schuetz. Human MDR1 and mouse mdr1a P-glycoprotein alter the cellular retention and disposition of erythromycin, but not of retinoic acid or benzo(a) pyrene. Arch. Biochem. Biophys. 350:340–347 (1998). A. H. Schinkel, E. Wagenaar, L. van Deemter, C. A. A. M. Mol, and P. Borst. Absence of the mdr1a P-glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J. Clin. Invest. 96:1698–1705 (1995). M. F. Fromm, R. B. Kim, C. M. Stein, G. R. Wilkinson, and D. M. Roden. Inhibition of P-glycoprotein-mediated drug transport: A unifying mechanism to explain the interaction between digoxin and quinidine. Circulation 99:552–557 (1999). P. J. Murrhy, T. L. Williams, R. E. McMahon, and F. J. Marshall. Metabolism of propionyl erythromycin lauryl sulfate. I. Fate of the propionyl erythromycin moiety in the rat. Drug Metab. Dispos. 3:155–163 (1975). R. B. Kim, M. F. Fromm, C. Wandel, B. Leake, A. J. J. Wood, D. M. Roden, and G. R. Wilkinson. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-I protease inhibitors. J. Clin. Invest. 101:289–294 (1998). G. W. Wilkinson and D. G. Shand. Commentary: A physiological approach to hepatic drug clearance. Clin. Pharmacol. Ther. 18:377–390 (1975). J. van Asperen, O. van Tellingen, and J. H. Beijnen. The role of mdr1a P-glycoprotein in the biliary and intestinal secretion of doxorubicin and vinblastine in mice. Drug Metab. Dispos. 28:264–267 (2000). P. B. Watkins. The barrier function of CYP3A4 and P-glycoprotein in the small bowel. Adv. Drug Deliv. Rev. 27:161–170 (1997).