Symposium Article: Molecular and Physical Mechanisms of First-Pass Extraction

Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues.

Thiebaut, F., Tsuruo, T., Hamada, H., Gottesman, M., Pastan, I., & Willingham, M. (1987) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.84.21.7735 · Cited by 2,823

Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians

Shimada, T., Yamazaki, H., Mimura, M., Inui, Y., & Guengerich, F. P. (1994) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22379-5 · Cited by 2,785

The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors.

Kim, R. B., Fromm, M. F., Wandel, C., Leake, B. F., Wood, A. J., Roden, D. M., & Wilkinson, G. R. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1269 · Cited by 1,054

Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P‐glycoprotein: Implications for drug delivery and activity in cancer chemotherapy

Wacher, V. J., Wu, C., & Benet, L. Z. (1995) · Molecular Carcinogenesis · doi:10.1002/mc.2940130302 · Cited by 855

Characterization of rat and human liver microsomal cytochrome P-450 forms involved in nifedipine oxidation, a prototype for genetic polymorphism in oxidative drug metabolism.

Guengerich, F. P., Martin, M. V., Beaune, P. H., Kremers, P. G., Wolff, T., & Waxman, D. J. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)89213-x · Cited by 724

Human P-glycoprotein transports cyclosporin A and FK506.

Saeki, T., Ueda, K., Tanigawara, Y., Hori, R., & Komano, T. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53221-x · Cited by 684

Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine*

Lown, K. S., Mayo, R. R., Leichtman, A. B., Hsiao, H.-L., Turgeon, D. K., Schmiedlin‐Ren, P., Brown, M. B., Guo, W.-S., Rossi, S. J., Benet, L. Z., et al. (1997) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(97)90027-8 · Cited by 679

Human P-glycoprotein transports cortisol, aldosterone, and dexamethasone, but not progesterone.

Ueda, K., Okamura, N., Hirai, M., Tanigawara, Y., Saeki, T., Kioka, N., Komano, T., & Hori, R. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35757-0 · Cited by 672

Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression.

Lown, K. S., Bailey, D. G., Fontana, R. J., Janardan, S. K., Adair, C. H., Fortlage, L. A., Brown, M. B., Guo, W., & Watkins, P. B. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119439 · Cited by 624

Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism*

Thummel, K. E., O’Shea, D., Paine, M. F., Shen, D. D., Kunze, K. L., Perkins, J. D., & Wilkinson, G. R. (1996) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(96)90177-0 · Cited by 615

Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4.

Kronbach, T., Mathys, D., Umeno, M., Gonzalez, F. J., & Meyer, U. (1989) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09118-7 · Cited by 532

Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes.

Kolars, J. C., Schmiedlin‐Ren, P., Schuetz, J. D., Fang, C., & Watkins, P. B. (1992) · Journal of Clinical Investigation · doi:10.1172/jci116064 · Cited by 528

Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man.

Watkins, P. B., Wrighton, S. A., Schuetz, E. G., Molowa, D. T., & Guzelian, P. S. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113156 · Cited by 480

Prediction of in vivo drug metabolism in the human liver from in vitro metabolism data

Iwatsubo, T., Hirota, N., Ooie, T., Suzuki, H., Shimada, N., Chiba, K., Ishizaki, T., Green, C. E., Tyson, C. A., & Sugiyama, Y. (1997) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(96)00184-2 · Cited by 479

First-pass metabolism of cyclosporin by the gut

Kolars, J. C., Watkins, P. B., Merion, R. M., & Awni, W. M. (1991) · The Lancet · doi:10.1016/0140-6736(91)92302-i · Cited by 423

Noninvasive tests of CYP3A enzymes

Watkins, P. B. (1994) · Pharmacogenetics · doi:10.1097/00008571-199408000-00001 · Cited by 413

Midazolam A Review of its Pharmacological Properties and Therapeutic Use

DUNDEE, J. W., Halliday, N. J., Harper, K. W., & Brogden, R. N. (1984) · Drugs · doi:10.2165/00003495-198428060-00002 · Cited by 357

Differentiation of absorption and first-pass gut and hepatic metabolism in humans: Studies with cyclosporine*

Wu, C.-Y., Benet, L. Z., Hébert, M. F., Gupta, S. K., Rowland, M., Gomez, D. Y., & Wacher, V. J. (1995) · Clinical Pharmacology & Therapeutics · doi:10.1016/0009-9236(95)90168-x · Cited by 356

Mechanisms of enhanced oral availability of CYP3A4 substrates by grapefruit constituents: Decreased enterocyte CYP3A4 concentration and mechanism-based inactivation by furanocoumarins

Hollenberg, P. F., Edwards, D. J., He, K., Fitzsimmons, M. E., Fisher, J. M., Rahman, A., Thummel, K. E., Lown, K. S., Woster, P. M., Schmiedlin‐Ren, P., et al. (2019) · PubMed · doi:10.17615/k2j5-jx75 · Cited by 349

Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction

Hébert, M. F., Roberts, J. P., Prueksaritanont, T., & Benet, L. Z. (1992) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1992.171 · Cited by 337

First-pass metabolism of midazolam by the human intestine*

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. (1996) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(96)90162-9 · Cited by 323

Efficient inhibition of P-glycoprotein-mediated multidrug resistance with a monoclonal antibody.

Mechetner, E. B., & Roninson, I. B. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.13.5824 · Cited by 322

Pleiotropic phenotype of colchicine‐resistant CHO cells: Cross‐resistance and collateral sensitivity

Bech‐Hansen, N. T., Till, J. E., & Ling, V. W. T. (1976) · Journal of Cellular Physiology · doi:10.1002/jcp.1040880104 · Cited by 314

Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel: Lack of prediction by the erythromycin breath test

Watkins, P. B., Wrighton, S. A., Barnett, J. L., Lown, K. S., Kunze, K. L., Thummel, K. E., & Kolars, J. C. (2019) · Carolina Digital Repository (University of North Carolina at Chapel Hill) · doi:10.17615/n8xg-qs69 · Cited by 304

The effects of ketoconazole on the intestinal metabolism and bioavailability of cyclosporine*

Gomez, D. Y., Wacher, V. J., Tomlanovich, S. J., Hébert, M. F., & Benet, L. Z. (1995) · Clinical Pharmacology & Therapeutics · doi:10.1016/0009-9236(95)90067-5 · Cited by 279

Oxidation of dihydropyridine calcium channel blockers and analogs by human liver cytochrome P-450 IIIA4

Guengerich, F. P., Brian, W. R., Iwasaki, M., Sari, M.-A., Baeaernhielm, C., & Berntsson, P. (1991) · Journal of Medicinal Chemistry · doi:10.1021/jm00110a012 · Cited by 261

Possible Involvement of Multiple P-Glycoprotein-Mediated Efflux Systems in the Transport of Verapamil and Other Organic Cations Across Rat Intestine

Saitoh, H., & Aungst, B. J. (1995) · Pharmaceutical Research · doi:10.1023/a:1016217505990 · Cited by 158

The function of Gp170, the multidrug-resistance gene product, in the brush border of rat intestinal mucosa

Hsing, S., Gatmaitan, Z., & Arias, I. M. (1992) · Gastroenterology · doi:10.1016/0016-5085(92)90173-v · Cited by 146

The effect of water-soluble vitamin E on cyclosporine pharmacokinetics in healthy volunteers*

Chang, T. T., Benet, L. Z., & Hébert, M. F. (1996) · Clinical Pharmacology & Therapeutics · doi:10.1016/s0009-9236(96)80007-5 · Cited by 122

Excretion and metabolism of 14C-midazolam in humans following oral dosing.

Heizmann, P., & Ziegler, W. H. (1981) · PubMed · Cited by 117

Felodipine kinetics in healthy men

Edgar, B., Regårdh, C. G., Johnsson, G., Johansson, L., Lundborg, P. G., Löfberg, I., & Rönn, O. (1985) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.1985.160 · Cited by 111

Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel. Lack of prediction by the erythromycin breath test.

Lown, K. S., Kolars, J. C., Thummel, K. E., Barnett, J. L., Kunze, K. L., Wrighton, S. A., & Watkins, P. B. (1994) · Drug Metabolism and Disposition · doi:10.1016/s0090-9556(25)08440-5 · Cited by 103

P‐glycoprotein‐mediated transcellular transport of MDR‐reversing agents

SAEKI, T., Ueda, K., Tanigawara, Y., Hori, R., & Komano, T. (1993) · FEBS Letters · doi:10.1016/0014-5793(93)81540-g · Cited by 91

Ketoconazole Effectively Reverses Multidrug Resistance in Highly Resistant KB Cells

Siegsmund, M. J., CARDARELLI, C. O., Aksentijevich, I., Sugimoto, Y., Pastan, I. H., & Gottesman, M. M. (1994) · The Journal of Urology · doi:10.1016/s0022-5347(17)34999-6 · Cited by 84

Pharmacokinetics of felodipine in patients with liver disease

Reg�rdh, C. G., Edgar, B., Olsson, R., Kendall, M. J., Collste, P., & Shansky, C. W. (1989) · European Journal of Clinical Pharmacology · doi:10.1007/bf00558072 · Cited by 54

From amplification to function: the case of the MDR1 gene

Roninson, I. B. (1992) · Mutation Research/Reviews in Genetic Toxicology · doi:10.1016/0165-1110(92)90005-t · Cited by 52

Reversal of drug resistance by erythromycin: Erythromycin increases the accumulation of actinomycin d and doxorubicin in multidrug‐resistant cells

Hofsli, E., & Nissen‐meyer, J. (1989) · International Journal of Cancer · doi:10.1002/ijc.2910440126 · Cited by 46

Contribution of the intestine to the first-pass metabolism of felodipine in the rat.

Wang, S. X., Sutfin, T. A., Bäärnhielm, C., & Regårdh, C. G. (1989) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)22256-x · Cited by 21

Interindividual variation in intestinal mdr1 expression: lack of short term diet effects

Fontana, R. (1995) · Gastroenterology · doi:10.1016/0016-5085(95)27260-7 · Cited by 9

Enterohepatic Circulation

Roberts, M. S., Magnusson, B. M., Burczynski, F. J., & Weiß, M. (2002) · Clinical Pharmacokinetics · doi:10.2165/00003088-200241100-00005 · Cited by 684

Inhibition and induction of human cytochrome P450 enzymes: current status

Pelkonen, O., Turpeinen, M., Hakkola, J., Honkakoski, P., Hukkanen, J., & Raunio, H. (2008) · Archives of Toxicology · doi:10.1007/s00204-008-0332-8 · Cited by 571

Cytochrome P450-mediated metabolism in the human gut wall

Thelen, K., & Dressman, J. (2009) · Journal of Pharmacy and Pharmacology · doi:10.1211/jpp.61.05.0002 · Cited by 338

Physicochemical Space for Optimum Oral Bioavailability: Contribution of Human Intestinal Absorption and First-Pass Elimination

Varma, M. V. S., Obach, R. S., Rotter, C. J., Miller, H., Chang, G., Steyn, S. J., El‐Kattan, A. F., & Troutman, M. D. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm901371v · Cited by 349

Gut reactions: Breaking down xenobiotic–microbiome interactions

Clarke, G., Sandhu, K. V., Griffin, B. T., Dinan, T. G., Cryan, J. F., & Hyland, N. P. (2019) · Pharmacological Reviews · doi:10.1124/pr.118.015768 · Cited by 319

Abstracts of Symposium Presentations (Monday)

(2001) · Drug Metabolism Reviews · doi:10.1081/dmr-100106270

Abstracts of Symposium Presentations (Thursday)

(2001) · Drug Metabolism Reviews · doi:10.1081/dmr-100106329

Abstracts of Symposium Presentations (Tuesday)

(2001) · Drug Metabolism Reviews · doi:10.1081/dmr-100106289

Abstracts of Symposium Presentations (Wednesday)

(2001) · Drug Metabolism Reviews · doi:10.1081/dmr-100106303

First-pass metabolism.

Brodie, M. J. (1983) · PubMed · Cited by 20