Loss of orally administered drugs in GI tract

Saudi Pharmaceutical Journal

Volumn 20, Issue 4, 2012, Pages 331-344

  Gavhane, Yogeshkumar Nanasaheb ^a   Yadav, Adhikrao Vyankatrao ^b  

^a Govt College of Pharmacy   (India)

^b Gaurishankar Education Society's Inst of Pharmaceutical Education and Research   (India)

Author keywords

CYP3A4; Cytochrome P450; Drug drug interaction; Efflux transporters; Gut wall mucosal enzymes; P glycoprotein

Indexed keywords

ALBENDAZOLE SULFOXIDE; AMIODARONE; CARBAMAZEPINE; CYCLOSPORIN; CYTOCHROME P450; DEXAMETHASONE; DILTIAZEM; ERYTHROMYCIN; ETOPOSIDE; FELODIPINE; INDINAVIR; ITRACONAZOLE; IVERMECTIN; KETOCONAZOLE; LIDOCAINE; MIDAZOLAM; MULTIDRUG RESISTANCE PROTEIN; NIFEDIPINE; NITRENDIPINE; PROGESTERONE; QUINIDINE; RAPAMYCIN; SAQUINAVIR; TACROLIMUS; TAMOXIFEN; TERFENADINE; TOFISOPAM; TRAMAZOLINE; UNINDEXED DRUG; VERAPAMIL;

AREA UNDER THE CURVE; ARTICLE; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG TRANSPORT; ENZYME SUBSTRATE; FIRST PASS EFFECT; FOOD DRUG INTERACTION; GASTROINTESTINAL TRACT FUNCTION; GRAPEFRUIT JUICE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INTESTINE ABSORPTION; INTESTINE MUCOSA; LIVER METABOLISM; NONHUMAN; ORAL DRUG ADMINISTRATION;

EID: 84866757253     PISSN: 13190164     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jsps.2012.03.005     Document Type: Article

References (124)

1. Ambudkar S., et al. Biochemical, cellular and pharmacological aspects of multidrug transporter. Annu. Rev. Phrmacol. Toxicol. 1999, 39:361-398.
2. Aoyama T., et al. Cyt. P 450 hPCN3, a novel cytochrome P-450 3A gene product that is differentially expressed in human adult liver. J. Biol. Chem. 1989, 264:10295-10388.
3. Artursson P. Epithelial transport of drugs in cell cultures. I: a model for studying the passive diffusion of drugs over intestinal absorptive (CaCo-2) cells. J. Pharm. Sci. 1990, 79:476-482.
4. Artursson P., Karlsson J. Correlation between oral drug absorption in human intestinal epithelial (Caco-2) cells. Biochem. Biophys. Res. Commun. 1991, 175:880-885.
5. Augustijns P., et al. Drug absorption studies of prodrug esters using the Caco-2 model: evaluation of ester hydrolysis and transepithelial transport. Int. J. Pharm. 1998, 166(1):45-53.
6. Augustins P., et al. Evidence for a polarized efflux system in Caco-2 cells capable of modulation of cyclosporine transport. Biochem. Biophys. Res. Commun. 1993, 197:360-365.
7. Back D., et al. The in vitro metabolism of ethinyl oestradiol, mestranol and levonorgestrel by human jejunal mucosa. Br. J. Clin. Pharmacol. 1981, 11:275-278.
8. Benet L., Cummins C. The drug efflux metabolism alliance: biochemical aspects. Adv. Drug Deliv. Rev. 2001, 50:53-511.
9. Benet L., et al. Intestinal drug metabolism and antitransport processes: a potential paradigm shift in oral drug delivery. J. Control Release 1996, 39:139-143.
10. Benet L., et al. Intestinal MDR Transport proteins and P450 enzyme as barriers to oral drug delivery. J. Control Release 1999, 62:25-31.
11. Benet L., et al. Unmasking the dynamic interplay between efflux transporters and metabolic enzymes. Int. J. Pharm. 2004, 277:3-9.
12. Beverly k., et al. Deconvulating the effects of P-GP on intestinal CYP3A a major challenge. Curr. Opin. Pharmacol. 2006, 6:528-532.
13. Biopharmaceutics and pharmacokinetics: A Treatise D. M. Bramhankar, Sunil B. Jaiswal Published by- M. K. Jain (Vallabh Prakashan) 1st ed. 1995, reprint - 2005.
14. Buchthal J., et al. Induction of cytochrome P450 1A by smoking or omeprazole in comparison with UDP glucoronosyl transferase in biopsies of human duodenal mucosa. Eur. J. Clin. Pharmacol. 1995, 47:431-435.
15. Burton P., et al. Evidence for a polarized efflux for peptides in the apical membrane of Caco-2 cells. Biochem. Biophys. Res. Commun. 1993, 190:760-766.
16. Cappiello M., et al. Distribution of UDP-glucoronyltransferase and its endogenous substrate uridine 5'-diphosphoglucuronic acid in human tissues. Eur. J. Clin. Pharmacol. 1991, 41:345-350.
17. Carrier V., et al. Intestinal responses to xenobiotics. Toxicol. In vitro 2001, 15:373-378.
18. Chen J., Pang K. Effect of flow on first-pass metabolism of drugs: single pass studies on 4-methylumbelliferone conjugation on the serially perfused rat intestine and liver preparations. J. Pharmacol. Exp. Ther. 1997, 280:24-31.
19. Cheng-Chung T., et al. Identification and localization of five CYP2Cs in murine extrahepatic tissues and their metabolism of arachidonic acid to regio- and stereoselective products. Pharmacol. Exp. Ther. 2001, 299(1):39-47.
20. Chi-Yuan W., et al. Differentiation of absorption and first pass gut and hepatic metabolism in humans; studies with cyclosporine. Clin. Pharmacol. Ther. 1995, 58:492-497.
21. Collett A., et al. Comparison of HT 29-18 C and Caco-2 cell lines as models for studying intestinal paracellular drug absorption. Pharm. Res. 1996, 13216-13221.
22. Crauste-Manciet S., et al. Cefpodoxime-proxetil hydrolysis and food effects in the intestinal lumen before absorption: in vitro comparison of rabbit and human material. Int. J. Pharm. 1997, 157(2):153-161.
23. Cummins C., et al. In vivo modulation of intestinal cyp3A metabolism by P-gP: studies using rat single pass intestinal perfusion model. J. Pharmacol. Exp. Ther. 2003, 305:306-314.
24. Cummins C., et al. CYP3A 4 - transfected Caco-2 cells as a tool for understanding biochemical absorption barriers. Studies with sirolimus and midazolam. J. Pharmacol. Exp. Ther. 2004, 308:143-155.
25. Dewaziers I., et al. Cytochrome P450 isozymes, epoxide hydrolase and glutathione transferases in rat and human hepatic and extrahepatic tissues. J. Pharmacol. Exp. Ther. 1990, 255:387-394.
26. Diczfaluzy E., et al. Formation of oestrone glucosiduronate by the human intestinal tract. Acta Endocrinol. 1962, 40:537-551.
27. Feng C., et al. Prodrugs of scutellarin: ethyl, benzyl and N,N-diethylglycolamide ester synthesis, physicochemical properties, intestinal metabolism and oral bioavailability in the rats. Eur. J. Pharm. Sci. 2006, 29(5):385-393.
28. Fitzsimmons M., Collins J. Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome P450 3A4. Drug Metab. Dispos. 1997, 25:256-266.
29. Franklin T., et al. Human colorectal carcinoma cells in vitro as a means to assess the metabolism of analogs of mycophenolic acid. Drug Metab. Dispos. 1997, 25(3):367-370.
30. Galetin A. Intestinal first-pass metabolism - bridging the gap between in vitro and in vivo (prediction of intestinal first-pass metabolism. Curr. Drug Metab. 2007, 6(7):643-644. (2).
31. Gomez D., et al. The effects of ketoconazole on the intestinal metabolism and bioavailability of cyclosporine. Clin. Pharmacol. Ther. 1995, 58:15-19.
32. Gorski J., et al. Regioselective biotransformation of midazolam by members of the cytochrome P450 3A (CYP3A) subfamily. Biochem. Pharmacol. 1994, 47:1643-1653.
33. Gracia M., et al. Intestinal elimination of albendazole sulfoxide: Pharmacokinetic effects of inhibitors. Int. J. Pharm. 2003, 263:123-132.
34. Gramette T., Oertel R. Intestinal secretion of intravenous talinol is inhibited by luminal R-verapamil. Clin. Pharmacol. Ther. 1999, 66:239-245.
35. Greiner E., et al. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J. Clin. Invest. 1999, 104:147-153.
36. Guerrero F., et al. Role of MDR and esterase-mediated metabolism in pyrethroid-resistant populations of Haematobia irritans (Diptera: Muscidae) in Brazil. J. Med. Entomol. 2006, 43(5):896-901.
37. Gupta S., et al. Erythromycin enhances the absorption of cyclosporine. Br. J. Clin. Pharmacol 1988, 25:401-402.
38. Gupta S., et al. Cyclosporine-erythromycin interaction in renal transplant patients. Br. J. Clin. Pharmacol 1989, 27:475-481.
39. Hall S., et al. Molecular and physical mechanisms of first pass extraction. Drug Metab. Dispos. 1999, 27:161-166.
40. Hebert M., et al. Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction. Clin. Pharmcol Ther. 1992, 52:453-455.
41. Her C., et al. Human jejunal estrogen sulfotransferase and dehydro epiandrosterone sulfotransferase. Immunochemical characterization of interindividual variation. Drug Metab. Dispos. 1996, 24:1328-1335.
42. Hickman, D. et al. (1995). Longitudinal distribution of arylanine N-acetyl transferases along the human small intestine. 155 8 250.
43. Hirunpanich V., et al. Inhibitory effect of docosahexaenoic acid (DHA) on the intestinal metabolism of midazolam: in vitro and in vivo studies in rats. Int. J. Pharm. 2008, 3; 351(1-2):133-143. 3.
44. Hoff M., et al. Functional polymorphism of the human multidrug resistance genes, multiple sequence variations and correlation of one allele with P-gp expression and activity in vivo. Proc. Natl. Acad. Sci. USA 2000, 97:3473-3478.
45. Hunter J., et al. Intestinal secretion of drugs. The role of P-glycoprotein and related drug efflux systems in limiting oral drug absorption. Adv. Drug Deliv. Rev. 1997, 25(2-3):129-157.
46. Hyun S., et al. Pharmacokinetics of sildenafil after intravenous and oral administration in rats. Hepatic and intestinal first pass effects. Int. J. Pharm. 2006, 320:64-70.
47. Ilett K., et al. Metabolism of drugs and other xenobiotics in the gut lumen and wall. Pharmacol. Ther. 1990, 46:93-97.
48. Ilett K., et al. Metabolism of drugs and other xenobiotics in the gut lumen and wall. Pharmacol. Ther. 1990, 46:67-93.
49. Janice H., Barry H. Intestinal secretion of drugs: the role of P-gp and related drug efficacy systems in limiting oral drug absorption. Adv. Drug Deliv. Rev. 1997, 25:129-157.
50. Jason A., et al. (2004) P-glycoprotein efflux inhibition by amphiphilic diblock copolymers: relationship between copolymer concentration and substrate hydrophobicity, 21 (8) 1489-1497.
51. Kanfer I., et al. Pharmacokinetics of oral decongestants. Pharmacotherapy 1993, 13:1165-1285.
52. Kim R., et al. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J. Clin. Invest. 1998, 101:289-294.
53. Kolars J., et al. First pass metabolism of cyclosporine by the gut. Lancet 1991, 338:1488-1490.
54. Kolars J., et al. Identification of rifampin- inducible P450III3A4 (CYP3A4) in human small bowel enterocytes. J. Clin. Invest. 1992, 90:1871-1888.
55. Kolars J., et al. CYP3A gene expression in human gut epithelium. Pharmacogenetics 1994, 4:247-259.
56. Krisha D., Klotz U. Extrahepatic metabolism of drugs in humans. Clin. Pharmacokinet. 1994, 26:144-160.
57. Kupferschimidt H., et al. Interaction between grapefruit juice and midazolam in humans. Clin. Pharmacol. Ther. 1995, 58:20-28.
58. Lacey L., et al. Single dose pharmacokinetics of sumatriptan in healthy volunteers. Eur. J. Clin. Pharmacol. 1995, 47:543-548.
59. Lahoz A., et al. Strategies to in vitro assessment of major human cyp enzyme activities by using liquid chromatography tandem mass spectrometry. Curr. Drug Metab. 2008, 9(1):12-19.
60. Lampen A., et al. Metabolism of the immunosuppressant tacrolimus in the small intestine: cytochrome P450, drug interactions, and interindividual variability. Drug Metab. Dispos. 1995, 23:1315-1324.
61. Lampen A., et al. Metabolism and transport of the macrolide immunosuppressant sirolimus in the small intestine. J. Pharmacol Exp. Ther. 1998, 23:1104-1112.
62. Lee V., Yamamoto A. Penetration and enzymatic barriers to peptide and protein absorption. Adv. Drug Deliv. Rev. 1990, 4:171-207.
63. Lee D., et al. Pharmacokinetics of omeprazole after intravenous and oral administration to rats with liver cirrhosis induced by dimethylnitrosamine. Indian J. Pharm. 2007, 330(1-2):37-44.
64. Leiweber F. Possible physiological roles of carboxylic acid hydrolases. Drug Metab. Dispos. 1987, 18:379-439.
65. Leveque D., Jehl F. P-glycoprotein and pharmacokinetics. Anticancer Res. 1995, 15:331-336.
66. Lin J., et al. Is the role of small intestine in first pass metabolism overemphasized?. Pharmacol. Rev. 1999, 51:135-157.
67. Lina L., Eileen M. Role of cytochrome P450 isoenzymes in metabolism of O6-benzylguanine: implications for dacarbazine activation. Clin. Cancer Res. 2001, 7:4239-4244.
68. Mahon W., et al. Metabolism of flurazepam by small intestine. Clin. Pharmacol. Ther. 1977, 22:228-233.
69. Mária T., et al. Tofisopam inhibits the pharmacokinetics of CYP3A4 substrate midazolam. Eur. J. Clin. Pharmacol. 2008, 64:93-94. Number 1 Publisher Springer Berlin / Heidelberg.
70. Mayer U., et al. Substantial excretion of digoxin via the intestinal mucosa and prevention of long-term digoxin accumulation in the brain by the mdr la P-gp. Br. J. Pharmacol. 1996, 119:1008-1044.
71. Mayer U., et al. Full blockade of intestinal P-gp and expensive inhibition of blood brain barrier P-gp by oral treatment of mice with PsC 833. J. Clin. Invest. 1997, 100:2430-2436.
72. Mckay J., et al. Xenobiotic metabolizing enzyme expression in colonic neoplasia. Gut 1993, 34:1234-1239.
73. Mckinnon R., et al. Characterization of CYP3A gene subfamily expression in human gastrointestinal tissues. Gut 1995, 36:259-267.
74. Meinl W., et al. Sulfotransferase forms expressed in human intestinal Caco-2 and TC7 cells at varying stages of differentiation and role in benzo[a]pyrene metabolism. Drug Metab. Dispos. 2008, 36(2):276-283.
75. Meunier V., et al. The human Intestinal epithelial cell line CaCo-2; pharmacological and pharmacokinetic applications. Cell Biol. Toxicol. 1995, 11:187-194.
76. Micuda S., et al. P-glycoprotein function and expression during obstructive cholestasis in rats. Eur. J. Gastroenterol. Hepatol. 2008, 20(5):404-412.
77. Murray G., et al. The immunocytochemical localization and distribution of Cytochrome P450 in normal human hepatic and extrahepatic tissues with a monoclonal antibody to human cytochrome P-450. Br. J. Pharmacol. 1988, 25:465-475.
78. Neurkar M., et al. The use of surfactants to enhance the permeability of peptides through Caco-2 cells by inhibition of an apically polarized efflux system. Pharm. Res. 1996, 13(4):528-534. (7).
79. Norris D., et al. The effect of physical barriers and properties on the oral absorption of particulates. Adv. Drug Deliv. Rev. 1998, 34:135-154.
80. Odgers W., et al. Nucleotide polymorphism in the 5' promoter region of esterase 6 in Drosophila melanogaster and its relationship to enzyme activity variation. Genetics 1995, 141(1):215-222.
81. Ogasawara A., et al. Effect of oral ketoconazole on intestinal first-pass effect of midazolam and fexofenadine in cynomolgus monkeys. Drug Metab. Dispos. 2007, 35(3):410-418.
82. Pacifici G., et al. Presystemic glucuronidation of morphine in humans and rhesus monkeys: sub cellular distribution of the UDP-glucoronyltransferase in the liver and intestine. Xenobiotica 1986, 16:123-128.
83. Pacifici G., et al. Methylation of captopril in human liver, kidney and intestine. Xenobiotica 1991, 21:1107-1112.
84. Pacifici G., et al. (+) and (-) terbutaline are sulphated at a higher rate in human intestine than in liver. Eur. J. Clin. Pharmacol. 1993, 45:483-487.
85. Pacifici G., et al. S-methyl transferases in human intestine: different distribution of the microsomal thiol methyl transferase and cytosolic thiopurine methyltransferase along the human bowel. Xenobiotica 1993, 23:671-679.
86. Paine M., et al. First pass metabolism of midazolam by the human intestine. Clin. Pharmacol. Ther. 1996, 60:14-24.
87. Paine M., et al. Characterization of inter and intra intestinal differences in human CYP-3A dependent metabolism. J. Pharmacol. Exp. Ther. 1997, 283:1552-1562.
88. Palkama V., et al. Effect of saquinavir on the pharmacokinetics and pharmacodynamics of oral and intravenous midazolam. Clin. Pharmacol. Ther. 1999, 66:33-39.
89. Pesola G., Walle T. Stereoselective sulfate conjugation of isoproterenol in humans: comparison of hepatic, intestinal and platelet activity. Chirality 1993, 5:602-609.
90. Peters W., Kerners P. Cytochromes P-450 in the intestinal mucosa of man. Biochem. Pharmacol. 1989, 38:1535-1538.
91. Peters W., et al. Biotransformation enzymes in human intestine: critical low levels in the colon. Gut 1991, 32:408-412.
92. Poet T., et al. In vitro rat hepatic and intestinal metabolism of the organophosphate pesticides chlorpyrifos and diazinon. Toxicol. Sci. 2003, 72(2):193-200.
93. Prueksaritanont T., et al. Comparative studies of drug metabolizing enzymes in dog, monkey and human small intestines and in caco-2 cells. Drug Metab. Dispos. 1996, 24:634-642.
94. Raoof A., et al. Extrahepatic glucuronidation of propofol in man: possible contribution of gut wall and kidney. Eur. J. Clin. Pharmacol. 1996, 50:91-96.
95. Rogers S., et al. Intestinal metabolism of ethinyl oestradiol and paracetamol in vitro studies using chambers. Br. J. Clin. Pharmacol. 1987, 23:727-734.
96. Sansone-Parsons A., et al. Effect of oral posaconazole on the pharmacokinetics of cyclosporine and tacrolimus. Pharmacotherapy 2007, 27(6):825-834.
97. Schinkel A., et al. Normal variability and altered pharmacokinetics in mice lacking mdr 1 type (drug transporting) P-glycoprotein. Proc. Natl. Acad. Sci. USA 1997, 94:4028-4033.
98. Schuetz E., et al. Regulation of human liver cytochrome P 450 family 3A in primary and continuous culture of human hepatocytes. Hepatology 1993, 18:1254-1262.
99. Shargel L., et al. Comprehensive Pharmacy Review Publication 2006, Lippincott Williams& Wilkins, 84. sixth ed.
100. Sparrenboom A., et al. Limited oral bioavailability and active epithelial excretion of paclitaxel caused by P-gp in the intestine. Proc. Natl. Acad. Sci. USA 1997, 94:2031-2035.
101. Tam Y. Individual variation in 1st pass metabolism. Clin. Pharmacokinet. 1993, 25:300-328.
102. Thummel, K., (1995). Modelling hepatic and intestinal metabolism of the CYP3A probe midazolam from in vitro data. AAPS symposium on prediction of metabolic clearance, bioavailability and drug interactions from in vitro-derived data. AAPS Tenth Annual Meeting and exposition. Miami Beach, FL.
103. Thummel K., et al. Oral first pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism. Clin. Pharmacol. Ther. 1996, 59:491-502.
104. Thummel K., et al. Enzyme catalyzed processes of first pass hepatic metabolism and intestinal drug extraction. Adv. Drug Deliv. Rev. 1997, 27:99-127.
105. Ueda K., et al. Human P-gp transports cortisol, aldosterone, and dexamethasone, but not progesterone. J. Biol. Chem. 1992, 267:24248-24252.
106. Van O., et al. Extrahepatic metabolism of sevoflurane in children undergoing orthotopic liver transplantation. Anesthesiology 2000, 92(3):683-686.
107. Vickers A., et al. Sites of biotransformation for the cyclosporine derivatives SDZ IMM 125 using human liver and kidney slices and intestine. Drug Metab. Dispos. 1995, 23:327-333.
108. Wacher V., et al. Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy. Mol. Carcinog. 1995, 13:129-134.
109. Wacher V., et al. Active secretion and enterocytic drug metabolism barriers to drug absorption. Adv. Drug Deliv. Rev. 1996, 20:99-112.
110. Wacher V., et al. Role of P-glycoprotein and cytochrome P450 3A in limiting oral absorption of peptides and peptidomimetics. J. Pharm sci. 1998, 87:1322-1330.
111. Wacher V., et al. Active secretion and enterocytic drug metabolism barriers to drug absorption. Adv. Drug Deliv. Rev. 2001, 46:89-102.
112. Walker S., et al. Inter-species comparison of liver and small intestinal microsomal metabolism of fluoranthene. Food Chem. Toxicol. 2006, 44:380-387.
113. Warner P., et al. Sumatriptan absorption from different regions of the human gastrointestinal tract. Pharm. Res. 1945, 12:138-143.
114. Watkins P. Non invasive tests of CYP3A enzymes. Pharmacogenetics 1994, 4:171-184.
115. Watkins P.B. The barrier functions of CYP3A4 and P-gp in the small bowel. Adv. Drug Deliv. Rev. 1997, 27:161-170.
116. Watkins P., et al. Identification of glucocorticoid inducible cytochromes P-450 in the intestinal mucosa of rats and man. J. Clin. Invest. 1987, 80:1029-1036.
117. Waziers D., et al. Cytochrome P450 isoenzymes, epoxide hydrolases and glutathione transferases in rat and human hepatic and extrahepatic tissues. J. Pharmacol. Exp. Ther. 1990, 253:387-394.
118. Woodcock D., et al. Reversal of multidrug resistance by surfactants. Br. J. Cancer 1992, 66:62-68.
119. Wrighton S., et al. Identification of a polymorphically expressed member of the human cytochrome P 450 family. Mol. Pharmacol. 1989, 36:97-105.
120. Wrighton S., et al. Studies on the expression and metabolic capabilities of human liver cytochrome P 400 345. Mol. Pharmcol. 1990, 38:207-213.
121. http://www.nursinglink.com/.../320-clinically-significant-drug-interaction-with-the-cytochrome-p450-
122. Yan Z., Caldwell G. Metabolism profiling and cytochrome P450 inhibition & induction in drug discovery. Curr. Top. Med. Chem. 2001, 1(5):403-425.
123. Zhag Q., et al. Characterization of human small intestinal cytochromes P 450. Drug Metab. Dispos. 1999, 27:804-809.
124. Zhang W., et al. Impact of curcumin-induced changes in P-glycoprotein and CYP3A expression on the pharmacokinetics of peroral celiprolol and midazolam in rats. Drug Metab. Dispos. 2007, 35(1):110-115.