![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 283, Issue 3, 1552-1562, 1997
Departments of
Pharmaceutics (M.F.P., M.K., J.M.F., D.D.S.,
K.E.T.),
Medicinal Chemistry (K.L.K.) and
Surgery (C.L.M., J.D.P.),
University of Washington, Seattle, Washington
Cytochrome P450 3A (CYP3A) metabolizes a diverse array of clinically
important drugs. For some of these (e.g., cyclosporine, verapamil, midazolam), CYP3A in the intestinal mucosa contributes to
their extensive and variable first-pass extraction. To further characterize this phenomenon, we measured CYP3A content and catalytic activity toward the probe substrate midazolam in mucosa isolated from
duodenal, jejunal and ileal sections of 20 human donor intestines. For
comparison, the same measurements were performed for 20 human donor
livers, eight of which were obtained from the same donors as eight of
the intestines. Excellent correlations existed between homogenate and
microsomal CYP3A content for the three intestinal regions. Median
microsomal CYP3A content was greatest in the duodenum and lowest in the
ileum (31 vs. 17 pmol/mg of protein). With respect to
midazolam 1
-hydroxylation kinetics, the median
Km for each intestinal region was similar to the
median hepatic Km, ~4 µM. In contrast, the
median Vmax decreased from liver to duodenum to
jejunum to ileum (850 vs. 644 vs. 426 vs. 68 pmol/min/mg). Intrinsic clearance
(Vmax/Km) followed a
similar trend for the intestinal regions; median duodenal intrinsic
clearance was comparable to hepatic intrinsic clearance (157 and 200 µl/min/mg, respectively). Vmax correlated with
CYP3A content for all tissues except the ileum. Duodenal and jejunal
Vmax and CYP3A content varied by >30-fold among
donors. Microsomes prepared from every other 1-foot section of six
intestines were also analyzed for CYP3A as well as for two coenzymes.
In general, CYP3A activity, CYP3A content and CYP reductase activity
rose slightly from duodenum to middle jejunum and then declined to
distal jejunum and ileum. Cytochrome b5 content and cytochrome b5 reductase activity varied
little throughout the intestinal tract. Regional intrinsic midazolam
1-hydroxylation clearance was greatest for the jejunum, followed by
the duodenum and ileum (144, 50 and 19 ml/min, respectively).
Collectively, these results demonstrate that the upper small intestine
serves as the major site for intestinal CYP3A-mediated first-pass
metabolism and provides a rationale for interindividual differences in
oral bioavailability for some CYP3A substrates.
This article has been cited by other articles:
|
|
 |
|
  N. Ngo, Z. Yan, T. N. Graf, D. R. Carrizosa, A. D. M. Kashuba, E. C. Dees, N. H. Oberlies, and M. F. Paine Identification of a Cranberry Juice Product that Inhibits Enteric CYP3A-Mediated First-Pass Metabolism in Humans Drug Metab. Dispos., March 1, 2009; 37(3): 514 - 522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Ikemura, K. Urano, H. Matsuda, H. Mizutani, T. Iwamoto, and M. Okuda Decreased Oral Absorption of Cyclosporine A after Liver Ischemia-Reperfusion Injury in Rats: The Contribution of CYP3A and P-Glycoprotein to the First-Pass Metabolism in Intestinal Epithelial Cells J. Pharmacol. Exp. Ther., January 1, 2009; 328(1): 249 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. X. Garmire and C. A. Hunt In Silico Methods for Unraveling the Mechanistic Complexities of Intestinal Absorption: Metabolism-Efflux Transport Interactions Drug Metab. Dispos., July 1, 2008; 36(7): 1414 - 1424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. May, K. Westphal, T. Giessmann, D. Wegner, U. Adam, M. M. Lerch, R. Oertel, R. W. Warzok, W. Weitschies, M. Braeter, et al. Disposition and Antimuscarinic Effects of the Urinary Bladder Spasmolytics Propiverine: Influence of Dosage Forms and Circadian-Time Rhythms J. Clin. Pharmacol., May 1, 2008; 48(5): 570 - 579. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F Paine, W. W Widmer, S. N Pusek, K. L Beavers, A. B Criss, J. Snyder, and P. B Watkins Further characterization of a furanocoumarin-free grapefruit juice on drug disposition: studies with cyclosporine Am. J. Clinical Nutrition, April 1, 2008; 87(4): 863 - 871. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. W. Hong, I.-H. Lee, Y. H. Kwak, Y. T. Park, H. C. Sung, I. C. Kwon, and H. Chung Efficacy and tissue distribution of DHP107, an oral paclitaxel formulation Mol. Cancer Ther., December 1, 2007; 6(12): 3239 - 3247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Wortham, M. Czerwinski, L. He, A. Parkinson, and Y.-J. Y. Wan Expression of Constitutive Androstane Receptor, Hepatic Nuclear Factor 4{alpha}, and P450 Oxidoreductase Genes Determines Interindividual Variability in Basal Expression and Activity of a Broad Scope of Xenobiotic Metabolism Genes in the Human Liver Drug Metab. Dispos., September 1, 2007; 35(9): 1700 - 1710. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nishimura, N. Amano, Y. Kubo, M. Ono, Y. Kato, H. Fujita, Y. Kimura, and A. Tsuji Asymmetric Intestinal First-Pass Metabolism Causes Minimal Oral Bioavailability of Midazolam in Cynomolgus Monkey Drug Metab. Dispos., August 1, 2007; 35(8): 1275 - 1284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. O'Donnell, K. Grime, P. Courtney, D. Slee, and R. J. Riley The Development of a Cocktail CYP2B6, CYP2C8, and CYP3A5 Inhibition Assay and a Preliminary Assessment of Utility in a Drug Discovery Setting Drug Metab. Dispos., March 1, 2007; 35(3): 381 - 385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Shao, P. L. Stapleton, Y. S. Lin, and E. P. Gallagher Cytochrome P450 and Glutathione S-Transferase mRNA Expression in Human Fetal Liver Hematopoietic Stem Cells Drug Metab. Dispos., January 1, 2007; 35(1): 168 - 175. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. P. Duarte, B. B. Palma, A. A. Gilep, A. Laires, J. S. Oliveira, S. A. Usanov, J. Rueff, and M. Kranendonk The stimulatory role of human cytochrome b5 in the bioactivation activities of human CYP1A2, 2A6 and 2E1: a new cell expression system to study cytochrome P450-mediated biotransformation (a corrigendum report on Duarte et al. (2005) Mutagenesis 20, 93-100) Mutagenesis, January 1, 2007; 22(1): 75 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. H. Hinderling, A. H. Karara, B. Tao, M. Pawula, I. Wilding, and M. Lu Systemic Availability of the Active Metabolite Hydroxy-Fasudil After Administration of Fasudil to Different Sites of the Human Gastrointestinal Tract J. Clin. Pharmacol., January 1, 2007; 47(1): 19 - 25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zhou, E.-J. Poulton, F. Grun, T. K. Bammler, B. Blumberg, K. E. Thummel, and D. L. Eaton The Dietary Isothiocyanate Sulforaphane Is an Antagonist of the Human Steroid and Xenobiotic Nuclear Receptor Mol. Pharmacol., January 1, 2007; 71(1): 220 - 229. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M Iwase, N Kurata, R Ehana, Y Nishimura, T Masamoto, and H Yasuhara Evaluation of the effects of hydrophilic organic solvents on CYP3A-mediated drug-drug interaction in vitro Human and Experimental Toxicology, December 1, 2006; 25(12): 715 - 721. [Abstract] [PDF]
|
|
|
|
 |
|
 C.-c. Lin, C. Fang, S. Benetton, G.-f. Xu, and L.-T. Yeh Metabolic Activation of Pradefovir by CYP3A4 and Its Potential as an Inhibitor or Inducer. Antimicrob. Agents Chemother., September 1, 2006; 50(9): 2926 - 2931. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Liu, D. Tam, X. Chen, and K. S. Pang P-Glycoprotein and an Unstirred Water Layer Barring Digoxin Absorption in the Vascularly Perfused Rat Small Intestine Preparation: Induction Studies with Pregnenolone-16{alpha}-carbonitrile Drug Metab. Dispos., September 1, 2006; 34(9): 1468 - 1479. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Galetin and J. B. Houston Intestinal and Hepatic Metabolic Activity of Five Cytochrome P450 Enzymes: Impact on Prediction of First-Pass Metabolism J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 1220 - 1229. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rheeders, M. Bouwer, and T. C. Goosen Drug-drug interaction after single oral doses of the furanocoumarin methoxsalen and cyclosporine. J. Clin. Pharmacol., July 1, 2006; 46(7): 768 - 775. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F Paine, W. W Widmer, H. L Hart, S. N Pusek, K. L Beavers, A. B Criss, S. S Brown, B. F Thomas, and P. B Watkins A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine interaction Am. J. Clinical Nutrition, May 1, 2006; 83(5): 1097 - 1105. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Paine, H. L. Hart, S. S. Ludington, R. L. Haining, A. E. Rettie, and D. C. Zeldin THE HUMAN INTESTINAL CYTOCHROME P450 "PIE" Drug Metab. Dispos., May 1, 2006; 34(5): 880 - 886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Dai, M. F. Hebert, N. Isoherranen, C. L. Davis, C. Marsh, D. D. Shen, and K. E. Thummel EFFECT OF CYP3A5 POLYMORPHISM ON TACROLIMUS METABOLIC CLEARANCE IN VITRO Drug Metab. Dispos., May 1, 2006; 34(5): 836 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. M. Johnson, P. Zhang, J. D. Schuetz, and K. L. R. Brouwer CHARACTERIZATION OF TRANSPORT PROTEIN EXPRESSION IN MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN (MRP) 2-DEFICIENT RATS Drug Metab. Dispos., April 1, 2006; 34(4): 556 - 562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Xu, T. Hashizume, M. C. Shuhart, C. L. Davis, W. L. Nelson, T. Sakaki, T. F. Kalhorn, P. B. Watkins, E. G. Schuetz, and K. E. Thummel Intestinal and Hepatic CYP3A4 Catalyze Hydroxylation of 1{alpha},25-Dihydroxyvitamin D3: Implications for Drug-Induced Osteomalacia Mol. Pharmacol., January 1, 2006; 69(1): 56 - 65. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fakhoury, C. Litalien, Y. Medard, H. Cave, N. Ezzahir, M. Peuchmaur, and E. Jacqz-Aigrain LOCALIZATION AND mRNA EXPRESSION OF CYP3A AND P-GLYCOPROTEIN IN HUMAN DUODENUM AS A FUNCTION OF AGE Drug Metab. Dispos., November 1, 2005; 33(11): 1603 - 1607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Imai, M. Imoto, H. Sakamoto, and M. Hashimoto IDENTIFICATION OF ESTERASES EXPRESSED IN CACO-2 CELLS AND EFFECTS OF THEIR HYDROLYZING ACTIVITY IN PREDICTING HUMAN INTESTINAL ABSORPTION Drug Metab. Dispos., August 1, 2005; 33(8): 1185 - 1190. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Galetin, K. Ito, D. Hallifax, and J. B. Houston CYP3A4 Substrate Selection and Substitution in the Prediction of Potential Drug-Drug Interactions J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 180 - 190. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Rieder, A. P. Reiner, B. F. Gage, D. A. Nickerson, C. S. Eby, H. L. McLeod, D. K. Blough, K. E. Thummel, D. L. Veenstra, and A. E. Rettie Effect of VKORC1 Haplotypes on Transcriptional Regulation and Warfarin Dose N. Engl. J. Med., June 2, 2005; 352(22): 2285 - 2293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. D. Kharasch, K. E. Thummel, and P. B. Watkins CYP3A Probes Can Quantitatively Predict the In Vivo Kinetics of Other CYP3A Substrates and Can Accurately Assess CYP3A Induction and Inhibition Mol. Interv., June 1, 2005; 5(3): 151 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Duarte, B. B. Palma, A. Laires, J. S. Oliveira, J. Rueff, and M. Kranendonk Escherichia coli BTC, a human cytochrome P450 competent tester strain with a high sensitivity towards alkylating agents: involvement of alkyltransferases in the repair of DNA damage induced by aromatic amines Mutagenesis, May 1, 2005; 20(3): 199 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Paine, S. S. Ludington, M.-L. Chen, P. W. Stewart, S.-M. Huang, and P. B. Watkins DO MEN AND WOMEN DIFFER IN PROXIMAL SMALL INTESTINAL CYP3A OR P-GLYCOPROTEIN EXPRESSION? Drug Metab. Dispos., March 1, 2005; 33(3): 426 - 433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P. Duarte, B. B. Palma, A. A. Gilep, A. Laires, J. S. Oliveira, S. A. Usanov, J. Rueff, and M. Kranendonk The stimulatory role of human cytochrome b5 in the bioactivation activities of human CYP1A2, 2A6 and 2E1: a new cell expression system to study cytochrome P450 mediated biotransformation Mutagenesis, March 1, 2005; 20(2): 93 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Paine, A. B. Criss, and P. B. Watkins Two Major Grapefruit Juice Components Differ in Time to Onset of Intestinal CYP3A4 Inhibition J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 1151 - 1160. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Quintieri, C. Geroni, M. Fantin, R. Battaglia, A. Rosato, W. Speed, P. Zanovello, and M. Floreani Formation and Antitumor Activity of PNU-159682, A Major Metabolite of Nemorubicin in Human Liver Microsomes Clin. Cancer Res., February 15, 2005; 11(4): 1608 - 1617. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Galetin, C. Brown, D. Hallifax, K. Ito, and J. B. Houston UTILITY OF RECOMBINANT ENZYME KINETICS IN PREDICTION OF HUMAN CLEARANCE: IMPACT OF VARIABILITY, CYP3A5, AND CYP2C19 ON CYP3A4 PROBE SUBSTRATES Drug Metab. Dispos., December 1, 2004; 32(12): 1411 - 1420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Huang, Y. S. Lin, D. J. McConn II, J. C. Calamia, R. A. Totah, N. Isoherranen, M. Glodowski, and K. E. Thummel EVIDENCE OF SIGNIFICANT CONTRIBUTION FROM CYP3A5 TO HEPATIC DRUG METABOLISM Drug Metab. Dispos., December 1, 2004; 32(12): 1434 - 1445. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. McConn II, Y. S. Lin, K. Allen, K. L. Kunze, and K. E. Thummel DIFFERENCES IN THE INHIBITION OF CYTOCHROMES P450 3A4 AND 3A5 BY METABOLITE-INHIBITOR COMPLEX-FORMING DRUGS Drug Metab. Dispos., October 1, 2004; 32(10): 1083 - 1091. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Paine, A. B. Criss, and P. B. Watkins TWO MAJOR GRAPEFRUIT JUICE COMPONENTS DIFFER IN INTESTINAL CYP3A4 INHIBITION KINETIC AND BINDING PROPERTIES Drug Metab. Dispos., October 1, 2004; 32(10): 1146 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Abel, S. M. Opp, C. L. M. J. Verlinde, T. K. Bammler, and D. L. Eaton Characterization of Atrazine Biotransformation by Human and Murine Glutathione S-Transferases Toxicol. Sci., August 1, 2004; 80(2): 230 - 238. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Yasunami, H. Hara, T. Iwamura, T. Kataoka, and T. Adachi C-JUN N-TERMINAL KINASE MODULATES 1,25-DIHYDROXYVITAMIN D3-INDUCED CYTOCHROME P450 3A4 GENE EXPRESSION Drug Metab. Dispos., July 1, 2004; 32(7): 685 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Warrington, D. J. Greenblatt, and L. L. von Moltke The Effect of Age on P-Glycoprotein Expression and Function in the Fischer-344 Rat J. Pharmacol. Exp. Ther., May 1, 2004; 309(2): 730 - 736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Mouly, M. F. Paine, and P. B. Watkins Contributions of CYP3A4, P-glycoprotein, and Serum Protein Binding to the Intestinal First-Pass Extraction of Saquinavir J. Pharmacol. Exp. Ther., March 1, 2004; 308(3): 941 - 948. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Morimoto, T. Kotegawa, K. Tsutsumi, Y. Ohtani, H. Imai, and S. Nakano Effect of St. John's Wort on the Pharmacokinetics of Theophylline in Healthy Volunteers J. Clin. Pharmacol., January 1, 2004; 44(1): 95 - 101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Pang MODELING OF INTESTINAL DRUG ABSORPTION: ROLES OF TRANSPORTERS AND METABOLIC ENZYMES (FOR THE GILLETTE REVIEW SERIES) Drug Metab. Dispos., December 1, 2003; 31(12): 1507 - 1519. [Full Text] [PDF]
|
|
|
|
|
|
L. S. Kaminsky and Q.-Y. Zhang THE SMALL INTESTINE AS A XENOBIOTIC-METABOLIZING ORGAN Drug Metab. Dispos., December 1, 2003; 31(12): 1520 - 1525. [Full Text] [PDF]
|
|
|
|
|
|
J. C. Stevens, R. N. Hines, C. Gu, S. B. Koukouritaki, J. R. Manro, P. J. Tandler, and M. J. Zaya Developmental Expression of the Major Human Hepatic CYP3A Enzymes J. Pharmacol. Exp. Ther., November 1, 2003; 307(2): 573 - 582. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Veronese, L. P. Gillen, E. P. Dorval, W. W. Hauck, S. A. Waldman, and H. E. Greenberg Effect of Mibefradil on CYP3A4 In Vivo J. Clin. Pharmacol., October 1, 2003; 43(10): 1091 - 1100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. P. D. Lemahieu, B. D. Maes, Y. Ghoos, P. Rutgeerts, K. Verbeke, and Y. Vanrenterghem Measurement of hepatic and intestinal CYP3A4 and PGP activity by combined po + iv [14C]erythromycin breath and urine test Am J Physiol Gastrointest Liver Physiol, August 8, 2003; 285(3): G470 - G482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ito, K. Ogihara, S.-i. Kanamitsu, and T. Itoh PREDICTION OF THE IN VIVO INTERACTION BETWEEN MIDAZOLAM AND MACROLIDES BASED ON IN VITRO STUDIES USING HUMAN LIVER MICROSOMES Drug Metab. Dispos., July 1, 2003; 31(7): 945 - 954. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tamura, Y. Tokunaga, R. Ibuki, G. L. Amidon, H. Sezaki, and S. Yamashita The Site-Specific Transport and Metabolism of Tacrolimus in Rat Small Intestine J. Pharmacol. Exp. Ther., July 1, 2003; 306(1): 310 - 316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Westlind-Johnsson, S. Malmebo, A. Johansson, C. Otter, T. B. Andersson, I. Johansson, R. J. Edwards, A. R. Boobis, and M. Ingelman-Sundberg COMPARATIVE ANALYSIS OF CYP3A EXPRESSION IN HUMAN LIVER SUGGESTS ONLY A MINOR ROLE FOR CYP3A5 IN DRUG METABOLISM Drug Metab. Dispos., June 1, 2003; 31(6): 755 - 761. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Granvil, A.-M. Yu, G. Elizondo, T. E. Akiyama, C. Cheung, L. Feigenbaum, K. W. Krausz, and F. J. Gonzalez Expression of the Human CYP3A4 Gene in the Small Intestine of Transgenic Mice: In Vitro Metabolism and Pharmacokinetics of Midazolam Drug Metab. Dispos., May 1, 2003; 31(5): 548 - 558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Tam, R. G. Tirona, and K. S. Pang Segmental Intestinal Transporters and Metabolic Enzymes on Intestinal Drug Absorption Drug Metab. Dispos., April 1, 2003; 31(4): 373 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. L. Cummins, L. Salphati, M. J. Reid, and L. Z. Benet In Vivo Modulation of Intestinal CYP3A Metabolism by P-Glycoprotein: Studies Using the Rat Single-Pass Intestinal Perfusion Model J. Pharmacol. Exp. Ther., April 1, 2003; 305(1): 306 - 314. [Abstract] [Full Text]
|
|
|
|
|
|
T. S. Poet, H. Wu, A. A. Kousba, and C. Timchalk In Vitro Rat Hepatic and Intestinal Metabolism of the Organophosphate Pesticides Chlorpyrifos and Diazinon Toxicol. Sci., April 1, 2003; 72(2): 193 - 200. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. S. Burton, J. T. Goodwin, T. J. Vidmar, and B. M. Amore Predicting Drug Absorption: How Nature Made It a Difficult Problem J. Pharmacol. Exp. Ther., December 1, 2002; 303(3): 889 - 895. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.M.F. Kruijtzer, J.H. Beijnen, and J.H.M. Schellens Improvement of Oral Drug Treatment by Temporary Inhibition of Drug Transporters and/or Cytochrome P450 in the Gastrointestinal Tract and Liver: An Overview Oncologist, December 1, 2002; 7(6): 516 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. H.N. van Schaik, I. P. van der Heiden, J. N. van den Anker, and J. Lindemans CYP3A5 Variant Allele Frequencies in Dutch Caucasians Clin. Chem., October 1, 2002; 48(10): 1668 - 1671. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. N. Johnson, A. Rostami-Hodjegan, J. M. Goddard, M. S. Tanner, and G. T. Tucker Contribution of midazolam and its 1-hydroxy metabolite to preoperative sedation in children: a pharmacokinetic-pharmacodynamic analysis Br. J. Anaesth., September 1, 2002; 89(3): 428 - 437. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. S. Lin, A. L. S. Dowling, S. D. Quigley, F. M. Farin, J. Zhang, J. Lamba, E. G. Schuetz, and K. E. Thummel Co-Regulation of CYP3A4 and CYP3A5 and Contribution to Hepatic and Intestinal Midazolam Metabolism Mol. Pharmacol., July 1, 2002; 62(1): 162 - 172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Y. Li, G. L. Amidon, J. S. Kim, T. Heimbach, F. Kesisoglou, J. T. Topliss, and D. Fleisher Intestinal Metabolism Promotes Regional Differences in Apical Uptake of Indinavir: Coupled Effect of P-Glycoprotein and Cytochrome P450 3A on Indinavir Membrane Permeability in Rat J. Pharmacol. Exp. Ther., May 1, 2002; 301(2): 586 - 593. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. F. Paine, L. Y. Leung, H. K. Lim, K. Liao, A. Oganesian, M.-Y. Zhang, K. E. Thummel, and P. B. Watkins Identification of a Novel Route of Extraction of Sirolimus in Human Small Intestine: Roles of Metabolism and Secretion J. Pharmacol. Exp. Ther., April 1, 2002; 301(1): 174 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Thummel, C. Brimer, K. Yasuda, J. Thottassery, T. Senn, Y. Lin, H. Ishizuka, E. Kharasch, J. Schuetz, and E. Schuetz Transcriptional Control of Intestinal Cytochrome P-4503A by 1alpha ,25-Dihydroxy Vitamin D3 Mol. Pharmacol., December 1, 2001; 60(6): 1399 - 1406. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Oda and E. D. Kharasch Metabolism of Methadone and levo-alpha -Acetylmethadol (LAAM) by Human Intestinal Cytochrome P450 3A4 (CYP3A4): Potential Contribution of Intestinal Metabolism to Presystemic Clearance and Bioactivation J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 1021 - 1032. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yoshisue, S. Nagayama, T. Shindo, and Y. Kawaguchi Effects of 5-Fluorouracil on the Drug-Metabolizing Enzymes of the Small Intestine and the Consequent Drug Interaction with Nifedipine in Rats J. Pharmacol. Exp. Ther., June 1, 2001; 297(3): 1166 - 1175. [Abstract] [Full Text]
|
|
|
|
|
|
R. Yumoto, T. Murakami, M. Sanemasa, R. Nasu, J. Nagai, and M. Takano Pharmacokinetic Interaction of Cytochrome P450 3A-Related Compounds with Rhodamine 123, a P-Glycoprotein Substrate, in Rats Pretreated with Dexamethasone Drug Metab. Dispos., February 1, 2001; 29(2): 145 - 151. [Abstract] [Full Text]
|
|
|
|
|
|
I. Kawahara, Y. Kato, H. Suzuki, M. Achira, K. Ito, C. L. Crespi, and Y. Sugiyama Selective Inhibition of Human Cytochrome P450 3A4 by N-[2(R)-Hydroxy-1(S)-indanyl]-5-[2(S)-(1,1-dimethylethylaminocarbonyl)-4-[(furo[2,3-b]pyridin-5-yl)methyl]piperazin-1-yl]-4(S)-hydroxy-2(R)-phenylmethylpentanamide and P-glycoprotein by Valspodar in Gene Transfectant Systems Drug Metab. Dispos., October 1, 2000; 28(10): 1238 - 1243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. K. Yeung, D. H. Lang, K. E. Thummel, and A. E. Rettie Immunoquantitation of FMO1 in Human Liver, Kidney, and Intestine Drug Metab. Dispos., September 1, 2000; 28(9): 1107 - 1111. [Abstract] [Full Text]
|
|
|
|
 |
|
 T. E. Lackner Advances in Managing Overactive Bladder Journal of Pharmacy Practice, August 1, 2000; 13(4): 277 - 289. [Abstract] [PDF]
|
|
|
|
|
|
D. Cong, M. Doherty, and K. S. Pang A New Physiologically Based, Segregated-Flow Model to Explain Route-Dependent Intestinal Metabolism Drug Metab. Dispos., February 1, 2000; 28(2): 224 - 235. [Abstract] [Full Text]
|
|
|
|
|
|
J. H. Hochman, M. Chiba, J. Nishime, M. Yamazaki, and J. H. Lin Influence of P-Glycoprotein on the Transport and Metabolism of Indinavir in Caco-2 Cells Expressing Cytochrome P-450 3A4 J. Pharmacol. Exp. Ther., January 1, 2000; 292(1): 310 - 318. [Abstract] [Full Text]
|
|
|
|
|
|
W. Jacobsen, G. Kirchner, K. Hallensleben, L. Mancinelli, M. Deters, I. Hackbarth, K. Baner, L. Z. Benet, K.-F. Sewing, and U. Christians Small Intestinal Metabolism of the 3-Hydroxy-3-methylglutaryl-Coenzyme A Reductase Inhibitor Lovastatin and Comparison with Pravastatin J. Pharmacol. Exp. Ther., October 1, 1999; 291(1): 131 - 139. [Abstract] [Full Text]
|
|
|
|
|
|
S. Ekins, G. Bravi, J. H. Wikel, and S. A. Wrighton Three-Dimensional-Quantitative Structure Activity Relationship Analysis of Cytochrome P-450 3A4 Substrates J. Pharmacol. Exp. Ther., October 1, 1999; 291(1): 424 - 433. [Abstract] [Full Text]
|
|
|
|
|
|
Q.-Y. Zhang, D. Dunbar, A. Ostrowska, S. Zeisloft, J. Yang, and L. S. Kaminsky Characterization of Human Small Intestinal Cytochromes P-450 Drug Metab. Dispos., July 1, 1999; 27(7): 804 - 809. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. H. Lin, M. Chiba, and T. A. Baillie Is the Role of the Small Intestine in First-Pass Metabolism Overemphasized? Pharmacol. Rev., June 1, 1999; 51(2): 135 - 158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Gibbs, K. L. Kunze, W. N. Howald, and K. E. Thummel Effect of Inhibitor Depletion on Inhibitory Potency: Tight Binding Inhibition of CYP3A by Clotrimazole Drug Metab. Dispos., May 1, 1999; 27(5): 596 - 599. [Abstract] [Full Text]
|
|
|
|
|
|
J. M. Fisher, S. A. Wrighton, P. B. Watkins, P. Schmiedlin-Ren, J. C. Calamia, D. D. Shen, K. L. Kunze, and K. E. Thummel First-Pass Midazolam Metabolism Catalyzed by 1alpha ,25-Dihydroxy Vitamin D3-Modified Caco-2 Cell Monolayers J. Pharmacol. Exp. Ther., May 1, 1999; 289(2): 1134 - 1142. [Abstract] [Full Text]
|
|
|
|
|
|
J. M. Fisher, S. A. Wrighton, J. C. Calamia, D. D. Shen, K. L. Kunze, and K. E. Thummel Midazolam Metabolism by Modified Caco-2 Monolayers: Effects of Extracellular Protein Binding J. Pharmacol. Exp. Ther., May 1, 1999; 289(2): 1143 - 1150. [Abstract] [Full Text]
|
|
|
|
|
|
M. F. Paine, P. Schmiedlin-Ren, and P. B. Watkins Cytochrome P-450 1A1 Expression in Human Small Bowel: Interindividual Variation and Inhibition by Ketoconazole Drug Metab. Dispos., March 1, 1999; 27(3): 360 - 364. [Abstract] [Full Text]
|
|
|
|
|
|
M. A. Gibbs, K. E. Thummel, D. D. Shen, and K. L. Kunze Inhibition of Cytochrome P-450 3A (CYP3A) in Human Intestinal and Liver Microsomes: Comparison of Ki Values and Impact of CYP3A5 Expression Drug Metab. Dispos., February 1, 1999; 27(2): 180 - 187. [Abstract] [Full Text]
|
|
 |
 |
 |
|
 |
 |
 |
