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

Clinical Pharmacology and Therapeutics

Volumn 62, Issue 3, 1997, Pages 248-260

  Lown, Kenneth S ^b   Mayo, Robert R ^b   Leichtman, Alan B ^b   Hsiao, Hsiu Ling ^b   Turgeon, D Kim ^b   Schmiedlin Ren, Phyllissa ^b   Brown, Morton B ^b   Guo, Wensheng ^b   Rossi, Stephen J ^b   Benet, Leslie Z ^b   Watkins, Paul B ^a  

^a Urology Institute Case Medical Center University Hospitals   (United States)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOSPORIN; ERYTHROMYCIN; GLYCOPROTEIN P; LIVER ENZYME;

ADULT; AGED; ARTICLE; BIOAVAILABILITY; BREATH ANALYSIS; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DRUG CLEARANCE; DRUG TRANSPORT; ENDOSCOPY; ENZYME ACTIVITY; FEMALE; FIRST PASS EFFECT; GENE EXPRESSION; GENETIC VARIABILITY; HUMAN; HUMAN TISSUE; IMMUNOBLOTTING; INHALATIONAL DRUG ADMINISTRATION; INTESTINE; INTESTINE BIOPSY; KIDNEY TRANSPLANTATION; MALE; MULTIPLE REGRESSION; ORAL DRUG ADMINISTRATION; PRIORITY JOURNAL; QUANTITATIVE ASSAY;

ADMINISTRATION, ORAL; ADULT; AGED; AREA UNDER CURVE; BIOLOGICAL AVAILABILITY; BREATH TESTS; CYCLOSPORINE; CYTOCHROME P-450 ENZYME SYSTEM; DUODENUM; FEMALE; HUMANS; IMMUNOBLOTTING; IMMUNOSUPPRESSIVE AGENTS; KIDNEY TRANSPLANTATION; LIVER; MALE; MIDDLE AGED; MIXED FUNCTION OXYGENASES; P-GLYCOPROTEIN; REGRESSION ANALYSIS;

EID: 12644272784     PISSN: 00099236     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0009-9236(97)90027-8     Document Type: Article

References (56)

1. Pallardó LM, Sánchez P, Sánchez J, García J, Beneyto I, Orero E, et al. Analysis of the risk factors of late failure in renal transplantation under cyclosporine immunosuppression. Transplant Proc 1994;26:2536-7.
2. Ponticelli C, Tarantino A, Montagnino G. Controlled trials with cyclosporine in kidney transplantation. Transplant Proc 1994;26:2490-2.
3. Thiel G, Bock A, Spöndlin M, Brunner FP, Mihatsch M, Rufli T, et al. Long-term benefits and risks of cyclosporin A (sandimmun) - an analysis at 10 years. Transplant Proc 1994;26:2493-8.
4. Lindholm A, Henricsson S, Lind M, Dahlqvist R. Intraindividual variability in the relative systemic availability of cyclosporin after oral dosing. Eur J Clin Pharmacol 1988;34:461-4.
5. Lemaire M, Fahr A, Maurer G. Pharmacokinetics of cyclosporine: inter- and intra-individual variations and metabolic pathways. Transplant Proc 1990;22: 1110-2.
6. Kahan BD. Cyclosporine. N Engl J Med 1989;321: 1725-38.
7. Kronbach T, Fischer V, Meyer UA. Cyclosporine metabolism in human liver: identification of a cytochrome P-450III gene family as the major cyclosporine-metabolizing enzyme explains interactions of cyclosporine with other drugs. Clin Pharmacol Ther 1988;43:630-5.
8. Combalbert J, Fabre I, Fabre G, Dalet I, Derancourt J, Cano JP, et al. Metabolism of cyclosporin A; IV: purification and identification of the rifampicin-inducible human liver cytochrome P-450 (cyclosporin A oxidase) as a product of P450IIIA gene subfamily. Drug Metab Dispos 1989;17:197-207.
9. Aoyama T, Yamano S, Waxman DJ, Lapenson DP, Meyer UA, Fischer V, et al. Cytochrome P-450 hPCN3, a novel cytochrome P450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine. J Biol Chem 1989;264:10388-95.
10. Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP. 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. J Pharmacol Exp Ther 1994;270:414-23.
11. Guengerich FP, Martin MV, Beaune PH, Kremers P, Wolff T, Waxman DJ. Characterization of rat and human liver microsomal cytochrome P-450 forms involved in nifedipine oxidation, a prototype for genetic polymorphism in oxidative drug metabolism. J Biol Chem 1986;261:5051-60.
12. Wrighton SA, Thomas PE, Willis P, Maines SL, Watkins PB, Levin W, et al. Purification of a human liver cytochrome P-450 immunochemically related to several cytochromes P-450 purified from untreated rats. J Clin Invest 1987;80:1017-22.
13. Lown KS, Kolars JC, Thummel KE, Barnett JL, Kunze KL, Wrighton SA, et al. Interpatient heterogeneity in expression of CYP3A4 and CYP3A5 in small bowel: lack of prediction by the erythromycin breath test [published erratum appears in Drug Metab Dispos 1995;23:following table of contents]. Drug Metab Dispos 1994;22:947-55.
14. Thummel KE, Shen DD, Podoll TD, Kunze KL, Trager WF, Hartwell PS, et al. Use of midazolam as a human cytochrome P450 3A probe; I: in vitro-in vivo correlations in liver transplant patients. J Pharmacol Exp Ther 1994;271:549-56.
15. Watkins PB. Noninvasive tests of CYP3A enzymes. Pharmacogenetics 1994;4:171-84.
16. Turgeon DK, Normolle DP, Leichtman AB, Annesley TM, Smith DE, Watkins PB. Erythromycin breath test predicts oral clearance of cyclosporine in kidney transplant recipients. Clin Pharmacol Ther 1992;52: 471-8.
17. Watkins PB, Wrighton SA, Schuetz EG, Molowa DT, Guzelian PS. Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man. J Clin Invest 1987;80:1029-36.
18. Kolars JC, Schmiedlin-Ren P, Schuetz JD, Fang C, Watkins PB. Identification of rifampin-inducible P450IIIA4 (CYP3A4) in human small bowel enterocytes. J Clin Invest 1992;90:1871-8.
19. Kolars JC, Awni WM, Merion RM, Watkins PB. First-pass metabolism of cyclosporin by the gut. Lancet 1991;338:1488-90.
20. Hebert MF, Roberts JP, Prueksaritanont T, Benet LZ. Bioavailability of cyclosporine with concomitant rifampin administration is markedly less than predicted by hepatic enzyme induction. Clin Pharmacol Ther 1992;52:453-7.
21. Gomez DY, Wacher VJ, Tomlanovich SJ, Hebert MF, Benet LZ. The effects of ketoconazole on the intestinal metabolism and bioavailability of cyclosporine. Clin Pharmacol Ther 1995;58:15-9.
22. Wu CY, Benet LZ, Hebert MF, Gupta SK, Rowland M, Gomez DY, et al. Differentiation of absorption and first-pass gut and hepatic metabolism in humans: studies with cyclosporine. Clin Pharmacol Ther 1995; 58:492-7.
23. Chen C, Chin JE, Ueda K, Clark DP, Pastan I, Gottesman MM, et al. Internal duplication and homology with bacterial transport proteins in the mdr1 (P-glycoprotein) gene from multidrug-resistant human cells. Cell 1986;47:381-9.
24. Roninson IB. From amplification to function: the case of the MDR1 gene. Mutat Res 1992;276:151-61.
25. Schinkel AH, Borst P. Multidrug resistance mediated by P-glycoproteins. Sem Cancer Biol 1991;2:213-26.
26. Gottesman MM, Pastan I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu Rev Biochem 1993;62:385-427.
27. Saeki T, Ueda K, Tanigawara Y, Hori R, Komano T. Human P-glycoprotein transports cyclosporin A and FK506. J Biol Chem 1993;268:6077-80.
28. Tsuji A, Tamai I, Sakata A, Tenda Y, Terasaki T. Restricted transport of cyclosporin A across the blood-brain barrier by a multidrug transporter, P-glycoprotein. Biochem Pharmacol 1993;46:1096-9.
29. Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham MC. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci USA 1987; 84:7735-8.
30. Hsing S, Gatmaitan Z, Arias IM. The function of Gp170, the multidrug-resistance gene product, in the brush border of rat intestinal mucosa. Gastroenterology 1992;102:879-85.
31. Penny JI, Campbell FC. Active transport of benzo-[a]pyrene in apical membrane vesicles from normal human intestinal epithelium. Biochim Biophys Acta 1994;1226:232-6.
32. Saitoh H, Aungst BJ. Possible involvement of multiple P-glycoprotein-mediated efflux systems in the transport of verapamil and other organic cations across rat intestine. Pharm Res 1995;12:1304-10.
33. Lown KS, Fontana RJ, Schmiedlin-Ren P, Turgeon DK, Watkins PB. Interindividual variation in intestinal mdr1: lack of short term diet effects [abstract]. Gastroenterology 1995;108:A737.
34. Watkins PB, Murray SA, Winkelman LG, Heuman DM, Wrighton SA, Guzelian PS. Erythromycin breath test as an assay of glucocorticoid-inducible liver cytochromes P-450: studies in rats and patients. J Clin Invest 1989;83:688-97.
35. Baker AL, Kotake AN, Schoeller DA. Clinical utility of breath tests for the assessment of hepatic function. Semin Liver Dis 1983;3:318-29.
36. Lown K, Kolars J, Turgeon K, Merion R, Wrighton SA, Watkins PB. The erythromycin breath test selectively measures P450IIIA in patients with severe liver disease. Clin Pharmacol Ther 1992;51:229-38.
37. Turgeon DK, Leichtman AB, Lown KS, Normolle DP, Deeb GM, Merion RM, et al. P450 3A activity and cyclosporine dosing in kidney and heart transplant recipients. Clin Pharmacol Ther 1994;56:253-60.
38. Bonkovsky HL, Hauri HP, Marti U, Gasser R, Meyer UA. Cytochrome P450 of small intestinal epithelial cells. Immunochemical characterization of the increase in cytochrome P450 caused by phenobarbital. Gastroenterology 1985;88:458-67.
39. Beaune P, Kremers P, Letawe-Goujon F, Gielen JE. Monoclonal antibodies against human liver cytochrome P-450. Biochem Pharmacol 1985;34:3547-52.
40. Wrighton SA, Brian WR, Sari MA, Iwasaki M, Guengerich FP, Raucy JL, et al. Studies on the expression and metabolic capabilities of human liver cytochrome P450IIIA5 (HLp3). Mol Pharmacol 1990; 38:207-13.
41. Chin JE, Soffir R, Noonan KE, Choi K, Roninson IB. Structure and expression of the human MDR (P-glycoprotein) gene family. Mol Cell Biol 1989;9:3808-20.
42. Smit JJ, Schinkel AH, Mol CA, Majoor D, Mooi WJ, Jongsma AP, et al. Tissue distribution of the human MDR3 P-glycoprotein [see comments] [published erratum appears in Lab Invest 1995;72:following table of contents]. Lab Invest 1994;71:638-49.
43. West AB, Isaac CA, Carboni JM, Morrow JS, Mooseker MS, Barwick KW. Localization of villin, a cytoskeletal protein specific to microvilli, in human ileum and colon and in colonic neoplasms. Gastroenterology 1988;94:343-52.
44. Lown KS, Bailey DG, Fontana RJ, et al. Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. J Clin Invest 1977;99:2545-53.
45. Pichard L, Fabre I, Fabre G, Domergue J, Saint Aubert B, Mourad G, et al. Cyclosporin A drug interactions: screening for inducers and inhibitors of cytochrome P450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes. Drug Metab Dispos 1990;18:595-606.
46. Paine MF, Shen DD, Kunze KL, Perkins JD, Marsh CL, McVicar JP, et al. First-pass metabolism of midazolam by the human intestine. Clin Pharmacol Ther 1996;60:14-24.
47. Watkins PB, Turgeon DK, Saenger P, Lown KS, Kolars JC, Hamilton T, et al. Comparison of urinary 6-β-cortisol and the erythromycin breath test as measures of hepatic P450IIIA (CYP3A) activity. Clin Pharmacol Ther 1992;52:265-73.
48. Schuetz EG, Furuya KN, Schuetz JD. Interindividual variation in expression of P-glycoprotein in normal human liver and secondary hepatic neoplasms. J Pharmacol Exp Ther 1995;275:1011-8.
49. Lum BL, Kaubisch S, Yahanda AM, Adler KM, Jew L, Ehsan MN, et al. Alteration of etoposide pharmacokinetics and pharmacodynamics by cyclosporine in a phase I trial to modulate multidrug resistance. J Clin Oncol 1992;10:1635-42.
50. Wilson WH, Jamis-Dow C, Bryant G, Balis FM, Klecker RW, Bates SE, et al. Phase I and pharmacokinetic study of the multidrug resistance modulator dexverapamil with EPOCH chemotherapy. J Clin Oncol 1995;13:1985-94.
51. Boote DJ, Dennis IF, Twentyman PR, Osborne RJ, Laburte C, Hensel S, et al. Phase I study of etoposide with SDZ PSC 833 as a modulator of multidrug resistance in patients with cancer. J Clin Oncol 1996;14: 610-8.
52. Leu BL, Huang J. Inhibition of intestinal P-glycoprotein and effects on etoposide absorption. Cancer Chemother Pharmacol 1995;35:432-6.
53. Siegsmund MJ, Cardarelli C, Aksentijevich I, Sugimoto Y, Pastan I, Gottesman MM. Ketoconazole effectively reverses multidrug resistance in highly resistant KB cells. J Urol 1994; 151:485-91.
54. Gan LS, Moseley MA, Khosla B, Augustijns PF, Bradshaw TP, Hendren RW, et al. CYP3A-like cytochrome P450-mediated metabolism and polarized efflux of cyclosporin A in Caco-2 cells: interaction between the two biochemical barriers to intestinal transport. Drug Metab Dispos 1996;24:344-9.
55. Wacher VJ, Wu CY, Benet LZ. 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;13:129-34.
56. Schuetz EG, Beck WT, Schuetz JD. Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol Pharmacol 1996; 49:311-8.