Functional interaction of intestinal CYP3A4 and P-glycoprotein

Fundamental and Clinical Pharmacology

Volumn 18, Issue 6, 2004, Pages 621-626

  Kivistö, Kari T ^a   Niemi, Mikko ^a   Fromm, Martin F ^b  

^a DR MARGARETE FISCHER BOSCH INSTITUTE OF CLINICAL PHARMACOLOGY   (Germany)

^b UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

Absorption; Bioavailability; CYP3A4; P glycoprotein

Indexed keywords

ANTIBIOTIC AGENT; ANTIEMETIC AGENT; ANTIHISTAMINIC AGENT; ANTINEOPLASTIC AGENT; BETA ADRENERGIC RECEPTOR BLOCKING AGENT; BUNITROLOL; CALCIUM CHANNEL BLOCKING AGENT; CARDIOVASCULAR AGENT; CARVEDILOL; CELIPROLOL; CORTICOSTEROID; CYTOCHROME P450 3A4; DIGITOXIN; DILTIAZEM; DOCETAXEL; DRUG; ETOPOSIDE; GLYCOPROTEIN P; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMATINIB; IMMUNOSUPPRESSIVE AGENT; MIBEFRADIL; PACLITAXEL; PROTEINASE INHIBITOR; TALINOLOL; TENIPOSIDE; UNINDEXED DRUG; VERAPAMIL; VINBLASTINE; VINCRISTINE;

BIOTRANSFORMATION; DRUG ABSORPTION; DRUG BIOAVAILABILITY; ENZYME ACTIVITY; ENZYME REGULATION; ENZYME SUBSTRATE; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INTESTINE ABSORPTION; INTESTINE CELL; MUCOSAL IMMUNITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; REVIEW; XENOBIOTIC METABOLISM;

ADMINISTRATION, ORAL; ANIMALS; BIOLOGICAL AVAILABILITY; CLINICAL TRIALS; CYTOCHROME P-450 ENZYME SYSTEM; ENTEROCYTES; HUMANS; INTESTINAL ABSORPTION; INTESTINES; MODELS, ANIMAL; P-GLYCOPROTEIN; PHARMACOKINETICS;

EID: 9444267085     PISSN: 07673981     EISSN: None     Source Type: Journal    
DOI: 10.1111/j.1472-8206.2004.00291.x     Document Type: Review

References (43)

1. Kolars J.C., Lown K.S., Schmiedlin-Ren P. et al. CYP3A gene expression in human gut epithelium. Pharmacogenetics (1994) 4 247-259.
2. 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. USA (1987) 84 7735-7738.
3. Greiner B., Eichelbaum M., Fritz P. et al. The role of intestinal P-glycoprotein in the interaction of digoxin and rifampin. J. Clin. Invest. (1999) 104 147-153.
4. Wacher V.J., Wu C.Y., Benet L.Z. 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.
5. 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 (1996) 39 139-143.
6. Watkins P.B. The barrier function of CYP3A4 and P-glycoprotein in the small bowel. Adv. Drug Deliv. Rev. (1997) 27 161-170.
7. Benet L.Z., Izumi T., Zhang Y., Silverman J.A., Wacher V.J. Intestinal MDR transport proteins and P-450 enzymes as barriers to oral drug delivery. J. Control. Release (1999) 62 25-31.
8. Zhang Y., Benet L.Z. The gut as a barrier to drug absorption: combined role of cytochrome P450 3 A and P-glycoprotein. Clin. Pharmacokinet. (2001) 40 159-168.
9. Hochman J.H., Chiba M., Nishime J., Yamazaki M., Lin J.H. Influence of P-glycoprotein on the transport and metabolism of indinavir in Caco-2 cells expressing cytochrome P-450 3A4. J. Pharmacol. Exp. Ther. (2000) 292 310-318.
10. Hochman J.H., Chiba M., Yamazaki M., Tang C., Lin J.H. P-glycoprotein-mediated efflux of indinavir metabolites in Caco-2 cells expressing cytochrome P450 3A4. J. Pharmacol. Exp. Ther. (2001) 298 323-330.
11. Fromm M.F. The influence of MDR1 polymorphisms on P-glycoprotein expression and function in humans. Adv. Drug Deliv. Rev. (2002) 54 1295-1310.
12. Marzolini C., Paus E., Buclin T., Kim R.B. Polymorphisms in human MDR1 (P-glycoprotein): recent advances and clinical relevance. Clin. Pharmacol. Ther. (2004) 75 13-33.
13. Paine M.F., Khalighi M., Fisher J.M. et al. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J. Pharmacol. Exp. Ther. (1997) 283 1552-1562.
14. von Richter O., Burk O., Fromm M.F., Thon K.P., Eichelbaum M., Kivisto K.T. Cytochrome P450 3A4 and P-glycoprotein expression in human small intestinal enterocytes and hepatocytes: a comparative analysis in paired tissue specimens. Clin. Pharmacol. Ther. (2004) 75 172-183.
15. Kolars J.C., Awni W.M., Merion R.M., Watkins P.B. First-pass metabolism of cyclosporin by the gut. Lancet (1991) 338 1488-1490.
16. Hebert M.F., Roberts J.P., Prueksaritanont T., Benet L.Z. Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction. Clin. Pharmacol. Ther. (1992) 52 453-457.
17. Wu C.Y., Benet L.Z., Hebert M.F. et al. Differentiation of absorption and first-pass gut and hepatic metabolism in humans: studies with cyclosporine. Clin. Pharmacol. Ther. (1995) 58 492-497.
18. Fromm M.F., Busse D., Kroemer H.K., Eichelbaum M. Differential induction of prehepatic and hepatic metabolism of verapamil by rifampin. Hepatology (1996) 24 796-801.
19. Paine M.F., Shen D.D., Kunze K.L. et al. First-pass metabolism of midazolam by the human intestine. Clin. Pharmacol. Ther. (1996) 60 14-24.
20. Thummel K.E., O'Shea D., Paine M.F. et al. Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3A-mediated metabolism. Clin. Pharmacol. Ther. (1996) 59 491-502.
21. von Richter O., Greiner B., Fromm M.F. et al. Determination of in vivo absorption, metabolism, and transport of drugs by the human intestinal wall and liver with a novel perfusion technique. Clin. Pharmacol. Ther. (2001) 70 217-227.
22. Lin J.H., Chiba M., Baillie T.A. Is the role of the small intestine in first-pass metabolism overemphasized? Pharmacol. Rev. (1999) 51 135-158.
23. Dietrich C.G., Geier A., Oude Elferink R.P. ABC of oral bioavailability: transporters as gatekeepers in the gut. Gut (2003) 52 1788-1795.
24. Schwab M., Eichelbaum M., Fromm M.F. Genetic polymorphisms of the human MDR1 drug transporter. Annu. Rev. Pharmacol. Toxicol. (2003) 43 285-307.
25. Gottesman M.M., Fojo T., Bates S.E. Multidrug resistance in cancer: role of ATP-dependent transporters. Nat. Rev. Cancer (2002) 2 48-58.
26. Fromm M.F. Importance of P-glycoprotein for drug disposition in humans. Eur. J. Clin. Invest. (2003) 33(Suppl. 2) 6-9.
27. Lin J.H., Yamazaki M. Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin. Pharmacokinet. (2003) 42 59-98.
28. Lown K.S., Mayo R.R., Leichtman A.B. et al. Role of intestinal P-glycoprotein (mdr1) in interpatient variation in the oral bioavailability of cyclosporine. Clin. Pharmacol. Ther. (1997) 62 248-260.
29. Sparreboom A., van Asperen J., Mayer U. et al. Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc. Natl. Acad. Sci. USA (1997) 94 2031-2035.
30. Kim R.B., Fromm M.F., Wandel C. 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.
31. Hoffmeyer S., Burk O., von Richter O. et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc. Natl. Acad, Sci. USA (2000) 97 3473-3478.
32. Johne A., Köpke K., Gerloff T. et al. Modulation of steady-state kinetics of digoxin by haplotypes of the P-glycoprotein MDR1 gene. Clin. Pharmacol. Ther. (2002) 72 584-594.
33. Mouly S., Paine M.F. P-glycoprotein increases from proximal to distal regions of human small intestine. Pharm. Res. (2003) 20 1595-1599.
34. Lown K.S., Kolars J.C., Thummel K.E. et al. Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel. Lack of prediction by the erythromycin breath test. Drug Metab. Dispos. (1994) 22 947-955.
35. Fromm M.F. Importance of P-glycoprotein at blood-tissue barriers. Trends Pharmacol. Sci. (2004) 25 423-429.
36. Cummins C.L., Jacobsen W., Benet L.Z. Unmasking the dynamic interplay between intestinal P-glycoprotein and CYP3A4. J. Pharmacol. Exp. Ther. (2002) 300 1036-1045.
37. Can L.S., Moseley M.A., Khosla B. et al. CYP3A-like cytochrome P450-mediated metabolism and polarized efflux of cyclosporin A in Caco-2 cells. Drug Metab. Dispos. (1996) 24 344-349.
38. Johnson B.M., Charman W.N., Porter C.J. The impact of P-glycoprotein efflux on enterocyte residence time and enterocyte-based metabolism of verapamil. J. Pharm. Pharmacol. (2001) 53 1611-1619.
39. Ito K., Kusuhara H., Sugiyama Y. Effects of intestinal CYP3A4 and P-glycoprotein on oral drug absorption: theoretical approach. Pharm. Res. (1999) 16 225-231.
40. Mouly S.J., Paine M.F., Watkins P.B. Contributions of CYP3A4. P-glycoprotein, and serum protein binding to the intestinal first-pass extraction of saquinavir, J. Pharmacol. Exp. Ther. (2004) 308 941-948.
41. 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. (2003) 305 306-314.
42. Drescher S., Glaeser H., Murdter T., Hitzl M., Eichelbaum M., Fromm MF. P-glycoprotein-mediated intestinal and biliary digoxin transport in humans. Clin, Pharmacol. Ther. (2003) 73 223-231.
43. Lau Y.Y., Wu C.Y., Okochi H., Benet L.Z. Ex situ inhibition of hepatic uptake and efflux significantly changes metabolism: hepatic enzyme-transporter interplay. J. Pharmacol. Exp. Ther. (2004) 308 1040-1045.