P-glycoprotein, secretory transport, and other barriers to the oral delivery of anti-HIV drugs

Advanced Drug Delivery Reviews

Volumn 39, Issue 1-3, 1999, Pages 105-116

  Aungst, Bruce J ^a  

^a DUPONT COMPANY   (United States)

Author keywords

Absorption; Bioavailability; HIV protease inhibitor; Intestinal; MRP; Reverse transcriptase inhibitor

Indexed keywords

ABSORPTION; ANTIBIOTICS; ENZYME INHIBITION; MECHANICAL PERMEABILITY; METABOLISM; PROTEINS; SOLUBILITY; VIRUSES;

BIOAVAILABILITY; GLYCOPROTEINS; HUMAN IMMUNODEFICIENCY VIRUS (HIV);

CONTROLLED DRUG DELIVERY;

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; AZIDOPINE; CARRIER PROTEIN; CHLORPROMAZINE; CYCLOSPORIN; CYCLOSPORIN A; DAUNORUBICIN; DELAVIRDINE; DEXAMETHASONE; DIDANOSINE; DIGOXIN; DILTIAZEM; DOXORUBICIN; EFAVIRENZ; ETOPOSIDE; GLYCOPROTEIN P; INDINAVIR; INDOMETACIN; IVERMECTIN; LAMIVUDINE; MULTIDRUG RESISTANCE PROTEIN; NELFINAVIR; NEVIRAPINE; NICARDIPINE; NUCLEOSIDE DERIVATIVE; PROBENECID; PROGESTERONE; PROTEIN ANTIBODY; PROTEINASE INHIBITOR; QUINIDINE; RHODAMINE 123; RITONAVIR; RNA DIRECTED DNA POLYMERASE INHIBITOR; SAQUINAVIR; STAVUDINE; VALSPODAR; VERAPAMIL; VINBLASTINE; VINCRISTINE; ZALCITABINE; ZIDOVUDINE;

DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG SOLUBILITY; DRUG TRANSPORT; HUMAN; INTESTINE ABSORPTION; INTESTINE SECRETION; MEMBRANE TRANSPORT; NONHUMAN; PERMEABILITY BARRIER; PRIORITY JOURNAL; REVIEW;

EID: 0032843082     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0169-409X(99)00022-8     Document Type: Article

References (74)

1. Knupp C.A., Shyu W.C., Dolin R., Valentine F.T., McLaren C., Martin R.R., Pittman K.A., Barbhaiya R.H. Pharmacokinetics of didanosine in patients with acquired immunodeficiency syndrome or acquired immunodeficiency syndrome-related complex. Clin. Pharmacol. Ther. 49:1991;523-535.
2. Knupp C.A., Shyu W.C., Morgenthien E.A., Lee J.S., Barbhaiya R.H. Biopharmaceutics of didanosine in humans and in a model for acid-labile drugs, the pentagastrin-pretreated dog. Pharm. Res. 10:1993;1157-1164.
3. Taburet A.-M., Singlas E. Drug interactions with antiviral drugs. Clin. Pharmacokinet. 30:1996;385-401.
4. Rana K.Z., Dudley M.N. Clinical pharmacokinetics of stavudine. Clin. Pharmacokinet. 33:1997;276-284.
5. Devineni D., Gallo J.M. Zalcitabine clinical pharmacokinetics and efficacy. Clin. Pharmacokinet. 28:1995;351-360.
6. Blum M.R., Liao S.H.T., Good S.S., deMiranda P. Pharmacokinetics and bioavailability of zidovudine in humans. Amer. J. Med. 85:(suppl 2A):1988;189-194.
7. Roxane Laboratories (1998) Viramune prescribing information, in: Physician's Desk Reference, Medical Economics Co., Montvale, NJ.
8. Lin J.H. Human immunodeficiency virus protease inhibitors, from drug design to clinical studies. Adv. Drug Del. Rev. 27:1997;215-233.
9. Abbott Laboratories (1997) Norvir package insert.
10. Vella S., Floridia M. Saquinavir clinical pharmacology and efficacy. Clin. Pharmacokinet. 34:1998;189-201.
11. Roche Laboratories (1997) Fortovase package insert.
12. Hidalgo I.J., Raub T.J., Borchardt R.T. Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology. 96:1989;736-749.
13. Artursson P., Karlsson J. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochem. Biophys. Res. Commun. 175:1991;880-885.
14. Bramer S.L., Au J.L.-S., Wientjes M.G. Gastrointestinal and hepatic first-pass elimination of 2′,3′-dideoxyinosine in rats. J. Pharmacol. Exp. Ther. 265:1993;731-738.
15. Anderson B.D., Wygant M.B., Xiang T.-X., Waugh W.A., Stella V.J. Preformulation solubility and kinetic studies of 2′,3′-dideoxypurine nucleosides: potential anti-AIDS agents. Int. J. Pharm. 45:1988;27-37.
16. Yu H., Sinko P.J. Influence of the microporous substratum and hydrodynamics on resistances to drug transport in cell culture systems: calculation of intrinsic transport parameters. J. Pharm. Sci. 86:1997;1448-1457.
17. Pharmacia and Upjohn (1998) Rescriptor prescribing information, in: Physician's Desk Reference, Medical Economics Co., Montvale, NJ.
18. Rabel S.R., Maurin M.B., Rowe S.M., Hussain M. Determination of the pKa and pH-solubility behavior of an ionizable cyclic carbamate, (S)-6-chloro-4-(cyclopropylethynyl)-1,4-benzoxazin-2-one (DMP 266). Pharm. Devel. Technol. 1:1996;91-95.
19. Conradi R.A., Hilgers A.R., Ho N.F.H., Burton P.S. The influence of peptide structure on transport across Caco-2 cells. Pharm. Res. 8:1991;1453-1460.
20. Lin J.H., Chiba M., Balani S.K., Chen I.-W., Kwei G.Y.-S., Vastag K.J., Nishime J.A. Species differences in the pharmacokinetics and metabolism of indinavir, a potent human immunodeficiency virus protease inhibitor. Drug Metab. Disp. 24:1996;1111-1120.
21. Chiba M., Hensleigh M., Lin J.H. Hepatic and intestinal metabolism of indinavir, an HIV protease inhibitor, in rat and human microsomes. Biochem. Pharmacol. 53:1997;1187-1195.
22. Lin J.H., Chen I.-W., Vastag K.J., Ostovic D. pH-dependent oral absorption of L-735,524, a potent HIV protease inhibitor, in rats and dogs. Drug Metab. Disp. 23:1995;730-735.
23. Sudoh M., Pauletti G.M., Yao W., Moser W., Yokoyama A., Pasternak A., Sprengeler P.A., SmithIII A.B., Hirschmann R., Borchardt R.T. Transport characteristics of peptidomimetics. Effect of the pyrrolinone bioisostere on transport across Caco-2 cell monolayers. Pharm. Res. 15:1998;719-725.
24. Shetty B.V., Kosa M.B., Khalil D.A., Webber S. Preclinicalpharmacokinetics and distribution to tissue of AG1343, an inhibitor of human immunodeficiency virus type 1 protease. Antimicrob. Agents Chemother. 40:1996;110-114.
25. Longer M., Shetty B., Zamansky I., Tyle P. Preformulation studies of a novel protease inhibitor, AG1343. J. Pharm. Sci. 84:1995;1090-1093.
26. Kempf D.J., Marsh K.C., Denissen J.F., McDonald E., Vasavanonda S., Flentge C.A., Green B.E., Fino L., Park C.H., Kong X.-P., Wideburg N.E., Saldivar A., Ruiz L., Kati W.M., Sham H.L., Robins T., Stewart K.D., Hsu A., Plattner J.J., Leonard J.M., Norbeck D.W. ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans. Proc. Natl. Acad. Sci. 92:1995;2484-2488.
27. Alsenz J., Steffan H., Alex R. Active apical secretory efflux of the HIV protease inhibitors saquinavir and ritonavir in Caco-2 cell monolayers. Pharm. Res. 15:1998;423-428.
28. Aungst B.J. Novel formulation strategies for improving oral bioavailability of drugs with poor membrane permeation or presystemic metabolism. J. Pharm. Sci. 82:1993;979-987.
29. Hsing S., Gatmaitan Z., Arias I.M. The function of Gp170, the multidrug-resistance gene product, in the brush border of rat intestinal mucosa. Gastroenterology. 102:1992;879-885.
30. Hunter J., Jepson M.A., Tsuruo T., Simmons N.L., Hirst B.H. Functional expression of P-glycoprotein in apical membranes of human intestinal Caco-2 cells. J. Biol. Chem. 268:1993;14991-14997.
31. Seelig A. A general pattern for substrate recognition by P-glycoprotein. Eur. J. Biochem. 251:1998;252-261.
32. Hunter J., Hirst B.H., Simmons N.L. Drug absorption limited by P-glycoprotein-mediated secretory drug transport in human intestinal epithelial Caco-2 cell layers. Pharm. Res. 10:1993;743-749.
33. Zacherl J., Hamilton G., Thalhammer T., Riegler M., Cosentini E.P., Ellinger A., Bischof G., Schweitzer M., Teleky B., Koperna T., Wenzl E. Inhibition of P-glycoprotein-mediated vinblastine transport across HCT-8 intestinal carcinoma monolayers by verapamil, cyclosporin A and SDZ PSC833 in dependence on extracellular pH. Cancer Chemother. Pharmacol. 34:1994;125-132.
34. Augustijns P.F., Bradshaw T.P., Gan L.-S.L., Hendren R.W., Thakker D.R. Evidence for a polarized efflux system in Caco-2 cells capable of modulating cyclosporin A transport. Biochem. Biophys. Res. Commun. 197:1993;360-365.
35. Saitoh H., Hatakeyama M., Eguchi O., Oda M., Takada M. Involvement of intestinal P-glycoprotein in the restricted absorption of methylprednisolone from rat small intestine. J. Pharm. Sci. 87:1998;73-75.
36. Saitoh H., Aungst B.J. Possible involvement of multiple P-glycoprotein-mediated efflux systems in the transport of verapamil and other organic cations across rat intestine. Pharm. Res. 12:1995;1304-1310.
37. Leu B.-L., Huang J.-D. Inhibition of intestinal P-glycoprotein and effects on etoposide absorption. Cancer Chemother. Pharmacol. 35:1995;432-436.
38. Emi Y., Tsunashima D., Ogawara K.-I., Higaki K., Kimura T. Role of P-glycoprotein as a secretory mechanism in quinidine absorption from rat small intestine. J. Pharm. Sci. 87:1998;295-299.
39. Cavet M.E., West M., Simmons N.L. Transport and epithelial secretion of the cardiac glycoside, digoxin, by human intestinal epithelial (Caco-2) cells. Brit. J. Pharmacol. 118:1996;1389-1396.
40. Schinkel A.H., Mayer U., Wagenaar E., Mol C.A.A.M., vanDeemter L., Smit J.J.M., vanderValk M.A., Voordouw A.C., Spits H., vanTellingen O., Zijlmans J.M.J.M., Fibbe W.E., Borst P. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc. Natl. Acad. Sci. 94:1997;4028-4033.
41. Zaman G.J.R., Cnubben N.H.P., vanBladeren P.J., Evers R., Borst P. Transport of the glutathione conjugate of ethacrynic acid by the human multidrug resistance protein MRP. FEBS Lett. 391:1996;126-130.
42. Paulusma C.C., Bosma P.J., Zaman G.J.R., Bakker C.T.M., Otter M., Scheffer G.L., Scheper R.J., Borst P., OudeElferink P.J. Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene. Science. 271:1996;1126-1128.
43. Flens M.J., Zaman G.J.R., vanderValk P., Izquierdo M.A., Schroeijers A.B., Scheffer G.L., vanderGroep P., deHaas M., Meijer C.J.L.M., Scheper R.J. Tissue distribution of the multidrug resistance protein. Amer. J. Pathol. 148:1996;1237-1247.
44. Evers R., Zaman G.J.R., vanDeemter L., Jansen H., Calafat J., Oomen L.C.J.M., OudeElferink R.P.J., Borst P., Schinkel A.H. Basolateral localization and export activity of the human multidrug resistance-associated protein in polarized pig kidney cells. J. Clin. Invest. 97:1996;1211-1218.
45. Collington G.K., Hunter J., Allen C.N., Simmons N.L., Hirst B.H. Polarized efflux of 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein from cultured epithelial cell monolayers. Biochem. Pharmacol. 44:1992;417-424.
46. Fujita T., Yamada H., Fukuzumi M., Nishimaki A., Yamamoto A., Muranishi S. Calcein is excreted from the intestinal mucosal cell membrane by the active transport system. Life Sci. 60:1997;307-313.
47. OudeElferink R.P.J., Bakker C.T.M., Jansen P.L.M. Glutathione-conjugate transport by human colon adenocarcinoma cells (Caco-2 cells). Biochem. J. 290:1993;759-764.
48. Saitoh H., Gerard C., Aungst B.J. The secretory intestinal transport of some beta-lactam antibiotics and anionic compounds: a mechanism contributing to poor oral absorption. J. Pharmacol. Exp. Ther. 278:1996;205-211.
49. Gollapudi S., Kim C.H., Tran B.-N., Sangha S., Gupta S. Probenecid reverses multidrug resistance in multidrug resistance-associated protein-overexpressing HL60/AR and H69/AR cells but not in P-glycoprotein-overexpressing HL60/Tax and P388/ADR cells. Cancer Chemother. Pharmacol. 40:1997;150-158.
50. Draper M.P., Martell R.L., Levy S.B. Indomethacin-mediated reversal of multidrug resistance and drug efflux in human and murine cell lines overexpressing MRP, but not P-glycoprotein. Brit. J. Cancer. 75:1997;810-815.
51. Narasaki F., Oka M., Nakano R., Ikeda K., Fukuda M., Nakamura T., Soda H., Nakagawa M., Kuwano M., Kohno S. Human canalicular multispecific organic anion transporter (cMOAT) is expressed in human lung, gastric, and colorectal cancer cells. Biochem. Biophys. Res. Commun. 240:1997;606-611.
52. Turnheim K., Lauterbach F. Interaction between intestinal absorption and secretion of monoquaternary ammonium compounds in guinea pigs - a concept for the absorption kinetics of organic cations. J. Pharmacol. Exp. Ther. 212:1980;418-424.
53. Miyamoto Y., Ganapathy V., Leibach F.H. Transport of guanidine in rabbit intestinal brush-border membrane vesicles. Amer. J. Physiol. 255:1988;G85-G92.
54. Chun J.K., Zhang L., Piquette-Miller M., Lau E., Tong L.-Q., Giacomini K.M. Characterization of guanidine transport in human renal brush border membranes. Pharm. Res. 14:1997;936-941.
55. Karlsson J., Kuo S.-M., Ziemniak J., Artursson P. Transport of celiprolol across human intestinal epithelial (Caco-2) cells: mediation of secretion by multiple transporters including P-glycoprotein. Brit. J. Pharmacol. 110:1993;1009-1016.
56. Cavet M.E., West M., Simmons N.L. Fluoroquinolone (ciprofloxacin) secretion by human intestinal epithelial (Caco-2) cells. Brit. J. Pharmacol. 121:1997;1567-1578.
57. Anderle P., Niederer E., Rubas W., Hilgendorf C., Spahn-Langguth H., Wunderli-Allenspach H., Merkle H.P., Langguth P. P-glycoprotein (P-gp) mediated efflux in Caco-2 cell monolayers: the influence of culturing conditions and drug exposure on P-gp expression levels. J. Pharm. Sci. 87:1998;757-762.
58. Makhey V.D., Guo A., Norris D.A., Hu P., Yan J., Sinko P.J. Characterization of the regional intestinal kinetics of drug efflux in rat and human intestine and in Caco-2 cells. Pharm. Res. 15:1998;1160-1167.
59. Lennernas H., Regardh C.-G. Dose-dependent intestinal absorption and significant intestinal excretion (exsorption) of the β-blocker pafenolol in the rat. Pharm. Res. 10:1993;727-731.
60. vanAsperen J., vanTellingen O., Sparreboom A., Schinkel A.H., Borst P., Nooijen W.J., Beijnen J.H. Enhanced oral bioavailability of paclitaxel in mice treated with the P-glycoprotein blocker SDZ PSC833. Brit. J. Cancer. 76:1997;1181-1183.
61. Terao T., Hisanaga E., Sai Y., Tamai I., Tsuji A. Active secretion of drugs from the small intestinal epithelium in rats by P-glycoprotein functioning as an absorption barrier. J. Pharm. Pharmacol. 48:1996;1083-1089.
62. Schinkel A.H., Smit J.J.M., vanTellingen O., Beijnen J.H., Wagenaar E., vanDeemter L., Mol C.A.A.M., vanderValk M.A., Robanus-Maandag E.C., teRiele H.P.J., Berns A.J.M., Borst P. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell. 77:1994;491-502.
63. Sparreboom A., vanAsperen J., Mayer U., Schinkel A.H., Smit J.W., Meijer D.K.F., Borst P., Nooijen W.J., Beijnen J.H., vanTellingen O. Limited oral bioavailability and active epithelial excretion of paclitaxel (Taxol) caused by P-glycoprotein in the intestine. Proc. Natl. Acad. Sci. 94:1997;2031-2035.
64. Kim R.B., Fromm M.F., Wandel C., Leake B., Wood A.J.J., Roden D.M., Wilkinson G.R. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-protease inhibitors. J. Clin. Invest. 101:1998;289-294.
65. Lee C.G.L., Gottesman M.M., Cardarelli C.O., Ramachandra M., Jeang K.-J., Ambudkar S.V., Pastan I., Dey S. HIV-1 protease inhibitors are substrates for the MDR1 multidrug transporter. Biochemistry. 37:1998;3594-3601.
66. Kaldor S.W., Kalish V.J., DaviesII J.F., Shetty B.V., Fritz J.E., Appelt K., Burgess J.A., Campanale K.M., Chirgadze N.Y., Clawson D.K., Dressman B.A., Hatch S.D., Khalil D.A., Kosa M.B., Lubbehusen P.P., Muesing M.A., Patick A.K., Reich S.H., Su K.S., Tatlock J.H. Viracept (nelfinavir mesylate, AG1343): a potent, orally bioavailable inhibitor of HIV-1 protease. J. Med. Chem. 40:1997;3979-3985.
67. Yusa K., Oh-hara T., Yamazaki A., Tsukahara S., Satoh W., Tsuruo T. Cross-resistance to anti-HIV nucleoside analogs in multidrug-resistant human cells. Biochem. Biophys. Res. Commun. 169:1990;986-990.
68. Antonelli G., Turriziani O., Cianfriglia M., Riva E., Dong G., Fattorossi A., Dianzani F. Resistance of HIV-1 to AZT might also involve the cellular expression of multidrug resistance P-glycoprotein. Aids Res. Human Retrovir. 8:1992;1839-1844.
69. Merry C., Barry M.G., Mulcahy F., Halifax K.L., Back D.J. Saquinavir pharmacokinetics alone and in combination with nelfinavir in HIV-infected patients. AIDS. 11:1997;F117-F120.
70. 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. Molec. Carcinogen. 13:1995;129-134.
71. Schuetz E.G., Beck W.T., Schuetz J.D. Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Molec. Pharmacol. 49:1996;311-318.
72. Mazzanti R., Fantappie O., Kamimoto Y., Gatmaitan Z., Gentilini P., Arias I.M. Bile acid inhibition of P-glycoprotein-mediated transport in multidrug-resistant cells and rat liver canalicular membrane vesicles. Hepatology. 20:1994;170-176.
73. Buckingham L.E., Balasubramanian M., Emanuele R.M., Clodfelter K.E., Coon J.S. Comparison of Solutol HS 15, Cremophor EL and novel ethoxylated fatty acid surfactants as multidrug resistance modification agents. Int. J. Cancer. 62:1995;436-442.
74. Nerurkar M.M., Burton P.S., Borchardt R.T. The use of surfactants to enhance the permeability of peptides through Caco-2 cells by inhibition of an apically polarized efflux system. Pharm. Res. 13:1996;528-534.