Interaction of macrocyclic lactones with the multidrug transporters: The bases of the pharmacokinetics of lipid-like drugs

Current Drug Metabolism

Volumn 10, Issue 3, 2009, Pages 272-288

  Lespine, Anne ^a   Dupuy, J ^a   Alvinerie, M ^a   Comera, C ^b   Nagy, T ^c   Krajcsi, P ^c   Orlowski, S ^d  

^a CEMAGREF   (France)

^b INSERM   (France)

^c SOLVO BIOTECHNOLOGY   (Hungary)

^d CEA   (France)

Author keywords

ABC transporters; Anthelmintics; Lipophilic drugs; Macrocyclic lactones; Multidrug resistance; P glycoprotein

Indexed keywords

ABAMECTIN; ABC TRANSPORTER; ALBENDAZOLE SULFOXIDE; BENZIMIDAZOLE; BREAST CANCER RESISTANCE PROTEIN; DORAMECTIN; EPRINOMECTIN; GLYCOPROTEIN P; IMIDAZOLE DERIVATIVE; ITRACONAZOLE; IVERMECTIN; KETOCONAZOLE; LIPID; LOPERAMIDE; MACROLIDE; MOXIDECTIN; MULTIDRUG RESISTANCE PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 2; MULTIDRUG RESISTANCE PROTEIN 3; QUERCETIN; SELAMECTIN; VALSPODAR; VERAPAMIL; XENOBIOTIC AGENT;

ANTHELMINTIC ACTIVITY; ANTINEOPLASTIC ACTIVITY; AREA UNDER THE CURVE; CLINICAL TRIAL; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG EFFICACY; DRUG ELIMINATION; DRUG EXCRETION; DRUG HALF LIFE; DRUG HYPERSENSITIVITY; DRUG MECHANISM; DRUG POTENTIATION; DRUG PROTEIN BINDING; DRUG SAFETY; DRUG STRUCTURE; DRUG TRANSFORMATION; DRUG TRANSPORT; DRUG UPTAKE; ENZYME SUBSTRATE; GENETIC POLYMORPHISM; HUMAN; HYDROPHOBICITY; IN VIVO STUDY; INTESTINE ABSORPTION; INTESTINE SECRETION; LIPID ABSORPTION; LIPID TRANSPORT; LIPOPHILICITY; LOW DRUG DOSE; MAMMAL; NEMATODE; NEUROTOXICITY; NONHUMAN; ONCHOCERCIASIS; PARASITEMIA; PHARMACODYNAMICS; PHYSICAL CHEMISTRY; REVIEW; SEX DIFFERENCE; TISSUE DISTRIBUTION;

ABSORPTION; ANIMALS; ANTHELMINTICS; ATP-BINDING CASSETTE TRANSPORTERS; DRUG RESISTANCE, MULTIPLE; HUMANS; IVERMECTIN; LACTONES; LIPIDS; MACROCYCLIC COMPOUNDS; NEOPLASM PROTEINS; P-GLYCOPROTEIN;

EID: 65549110669     PISSN: 13892002     EISSN: None     Source Type: Journal    
DOI: 10.2174/138920009787846297     Document Type: Review

References (169)

1. McKellar, Q.A.; Benchaoui, H.A. Avermectins and milbemycins. J. Vet. Pharmacol. Ther., 1996, 19(5), 331-351.
2. McKellar, Q.A.; Jackson, F. Veterinary anthelmintics: old and new. Trends Parasitol., 2004, 20(10), 456-461.
3. Cotreau, M.M.; Warren, S.; Ryan, J.L.; Fleckenstein, L.; Vanapalli, S.R.; Brown, K.R.; Rock, D.; Chen, C.Y.; Schwertschlag, U.S. The antiparasitic moxidectin: safety, tolerability, and pharmacokinetics in humans. J. Clin. Pharmacol., 2003, 43(10), 1108-1115.
4. Carter, G.T.; Nietsche, J.A.; Hertz, M.R.; Williams, D.R.; Siegel, M.M.; Morton, G.O.; James, J.C.; Borders, D.B. LL-F28249 antibiotic complex: a new family of antiparasitic macrocyclic lactones. Isolation, characterization and structures of LL-F28249 alpha, beta, gamma, lambda. J. Antibiot. (Tokyo), 1988, 41(4), 519-529.
5. Forrester, S.G.; Prichard, R.K.; Beech, R.N. A glutamate-gated chloride channel subunit from Haemonchus contortus: expression in a mammalian cell line, ligand binding, and modulation of anthelmintic binding by glutamate. Biochem. Pharmacol., 2002, 63(6), 1061-1068.
6. Sheriff, J.C.; Kotze, A.C.; Sangster, N.C.; Hennessy, D.R. Effect of ivermectin on feeding by Haemonchus contortus in vivo. Vet. Parasitol., 2005, 128(3-4), 341-346.
7. Schulz-Key, H. Observations on the reproductive biology of Onchocerca volvulus. Acta Leiden, 1990, 59(1-2), 27-44.
8. Campbell, W.C. Ivermectin, an antiparasitic agent. Med. Res. Rev., 1993, 13(1), 61-79.
9. Molyneux, D.H.; Bradley, M.; Hoerauf, A.; Kyelem, D.; Taylor, M.J. Mass drug treatment for lymphatic filariasis and onchocerciasis. Trends Parasitol., 2003, 19(11), 516-522.
10. Kita, K.; Shiomi, K.; Omura, S. Advances in drug discovery and biochemical studies. Trends Parasitol., 2007, 23(5), 223-229.
11. Kaplan, R.M. Drug resistance in nematodes of veterinary importance: a status report. Trends Parasitol., 2004, 20(10), 477-481.
12. Osei-Atweneboana, M.Y.; Eng, J.K.; Boakye, D.A.; Gyapong, J.O.; Prichard, R.K. Prevalence and intensity of Onchocerca volvulus infection and efficacy of ivermectin in endemic communities in Ghana: a two-phase epidemiological study. Lancet, 2007, 369(9578), 2021-2029.
13. Hennessy, D.R.; Alvinerie, M.R. in Macrocyclic Lactones and Antiparasitic Therapy; Vercruysse, J.; Rew, R.S., Eds. CAB International, 2002, pp. 97-123.
14. Lifschitz, A.; Virkel, G.; Sallovitz, J.; Sutra, J.F.; Galtier, P.; Alvinerie, M.; Lanusse, C. Comparative distribution of ivermectin and doramectin to parasite location tissues in cattle. Vet. Parasitol., 2000, 87(4), 327-338.
15. Bousquet-Melou, A.; Mercadier, S.; Alvinerie, M.; Toutain, P.L. Endectocide exchanges between grazing cattle after pour-on administration of doramectin, ivermectin and moxidectin. Int. J. Parasitol., 2004, 34(11), 1299-1307.
16. Laffont, C.M.; Bousquet-Melou, A.; Bralet, D.; Alvinerie, M.; Fink-Gremmels, J.; Toutain, P.L. A pharmacokinetic model to document the actual disposition of topical ivermectin in cattle. Vet. Res., 2003, 34(4), 445-460.
17. Lespine, A.; Sutra, J.F.; Dupuy, J.; Alvinerie, M. Eprinomectin in goat: assessment of subcutaneous administration. Parasitol. Res., 2003, 89(2), 120-122.
18. Garg, R.; Kumar, R.R.; Yadav, C.L.; Banerjee, P.S. Duration of anthelmintic effect of three formulations of ivermectin (oral, injectable and pour-on) against multiple anthelmintic-resistant haemonchus contortus in sheep. Vet. Res. Commun., 2007, 31(6), 749-755.
19. Lallemand, E.; Lespine, A.; Alvinerie, M.; Bousquet-Melou, A.; Toutain, P.L. Estimation of absolute oral bioavailability of moxidectin in dogs using a semi-simultaneous method: influence of lipid co-administration. J. Vet. Pharmacol. Ther., 2007, 30(5), 375-380.
20. Lespine, A.; Chanoit, G.; Bousquet-Melou, A.; Lallemand, E.; Bassissi, M.F.; Alvinerie, M.; Toutain, P.L. Contribution of lymphatic transport to the systemic exposure of orally administered moxidectin in conscious lymph duct-cannulated dogs. Eur. J. Pharm. Sci., 2005, 27(1), 37-43.
21. Kerboeuf, D.; Hubert, J.; Cardinaud, B.; Blond-Riou, F. The persistence of the efficacy of injectable or oral moxidectin against Teladorsagia, Haemonchus and Trichostrongylus species in experimentally infected sheep. Vet. Rec., 1995, 137(16), 399-401.
22. Chiu, S.H.; Taub, R.; Sestokas, E.; Lu, A.Y.; Jacob, T.A. Comparative in vivo and in vitro metabolism of ivermectin in steers, sheep, swine, and rat. Drug Metab. Rev., 1987, 18(2-3), 289-302.
23. Lanusse, C.; Lifschitz, A.; Virkel, G.; Alvarez, L.; Sanchez, S.; Sutra, J.F.; Galtier, P.; Alvinerie, M. Comparative plasma disposition kinetics of ivermectin, moxidectin and doramectin in cattle. J. Vet. Pharmacol. Ther., 1997, 20(2), 91-99.
24. Zulalian, J.; Stout, S.J.; daCunha, A.R.; Garces, T.; Miller, P. Absorption, tissue distribution, metabolism, and excretion of moxidetin in cattle. J. Agric. Food Chem., 1994, 42(2), 381-387.
25. Craven, J.; Bjorn, H.; Hennessy, D.R.; Friis, C. The effects of body composition on the pharmacokinetics of subcutaneously injected ivermectin and moxidectin in pigs. J. Vet. Pharmacol. Ther., 2002, 25(3), 227-232.
26. Imperiale, F.A.; Busetti, M.R.; Suarez, V.H.; Lanusse, C.E. Milk excretion of ivermectin and moxidectin in dairy sheep: assessment of drug residues during cheese elaboration and ripening period. J. Agric. Food Chem., 2004, 52(20), 6205-6211.
27. Alvinerie, M.; Lacoste, E.; Sutra, J.F.; Chartier, C. Some pharmacokinetic parameters of eprinomectin in goats following pour-on administration. Vet. Res. Commun., 1999, 23(7), 449-455.
28. Alvinerie, M.; Sutra, J.F.; Galtier, P.; Mage, C. Pharmacokinetics of eprinomectin in plasma and milk following topical administration to lactating dairy cattle. Res. Vet. Sci., 1999, 67(3), 229-232.
29. Dupuy, J.; Chartier, C.; Sutra, J.F.; Alvinerie, M. Eprinomectin in dairy goats: dose influence on plasma levels and excretion in milk. Parasitol. Res., 2001, 87(4), 294-298.
30. Bassissi, M.F.; Alvinerie, M.; Lespine, A. Macrocyclic lactones: distribution in plasma lipoproteins of several animal species including humans. Comp. Biochem. Physiol. C Toxicol. Pharmacol., 2004, 138(4), 437-444.
31. Bassissi, M.F.; Alvinerie, M.; Martin, P.G.; Perret, B.; Lespine, A. Influence of dyslipidemia on moxidectin distribution in plasma lipoproteins and on its pharmacokinetics. Pharm. Res., 2006, 23(11), 2672-2680.
32. Alvinerie, M.; Dupuy, J.; Eeckhoutte, C.; Sutra, J.F.; Kerboeuf, D. In vitro metabolism of moxidectin in Haemonchus contortus adult stages. Parasitol. Res., 2001, 87(9), 702-704.
33. Lespine, A.; Martin, S.; Dupuy, J.; Roulet, A.; Pineau, T.; Orlowski, S.; Alvinerie, M. Interaction of macrocyclic lactones with P-glycoprotein: structure-affinity relationship. Eur. J. Pharm. Sci., 2007, 30(1), 84-94.
34. Sarkadi, B.; Homolya, L.; Szakacs, G.; Varadi, A. Human multidrug resistance ABCB and ABCG transporters: participation in a chemoimmunity defense system. Physiol. Rev., 2006, 86(4), 1179-1236.
35. Dano, K. Active outward transport of daunomycin in resistant Ehrlich ascites tumor cells. Biochim. Biophys. Acta, 1973, 323(3), 466-483.
36. Gottesman, M.M.; Pastan, I. Biochemistry of multidrug resistance mediated by the multidrug transporter. Annu. Rev. Biochem., 1993, 62385-427.
37. 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(21), 7735-7738.
38. Fromm, M.F. Importance of P-glycoprotein at blood-tissue barriers. Trends Pharmacol. Sci., 2004, 25(8), 423-429.
39. Schinkel, A.H.; Smit, J.J.M.; van Tellingen, O.; Beijnen, J.H.; Wagenaar, E.; van Deemter, L.; Mol, C.A.A.M.; van der Valk, M.A.; Robanus-Maandag, E.C.; te Riele, 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, 1994, 77(4), 491-502.
40. Lautier, D.; Canitrot, Y.; Deeley, R.G.; Cole, S.P. Multidrug resistance mediated by the multidrug resistance protein (MRP) gene. Biochem. Pharmacol., 1996, 52(7), 967-977.
41. Borst, P.; Evers, R.; Kool, M.; Wijnholds, J. The multidrug resistance protein family. Biochim. Biophys. Acta, 1999, 1461(2), 347-357.
42. Kruh, G.D.; Belinsky, M.G. The MRP family of drug efflux pumps. Oncogene, 2003, 22(47), 7537-7552.
43. Chang, T.H.; Hakamada, K.; Toyoki, Y.; Tsuchida, S.; Sasaki, M. Expression of MRP2 and MRP3 during liver regeneration after 90% partial hepatectomy in rats. Transplantation, 2004, 77(1), 22-27.
44. Buchler, M.; Konig, J.; Brom, M.; Kartenbeck, J.; Spring, H.; Horie, T.; Keppler, D. cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in hyperbilirubinemic mutant rats. J. Biol. Chem., 1996, 271(25), 15091-15098.
45. Doyle, L.A.; Ross, D.D. Multidrug resistance mediated by the breast cancer resistance protein BCRP (ABCG2). Oncogene, 2003, 22(47), 7340-7358.
46. Jonker, J.W.; Merino, G.; Musters, S.; van Herwaarden, A.E.; Bolscher, E.; Wagenaar, E.; Mesman, E.; Dale, T.C.; Schinkel, A.H. The breast cancer resistance protein BCRP (ABCG2) concentrates drugs and carcinogenic xenotoxins into milk. Nat. Med., 2005, 11(2), 127-129.
47. Chen, Z.S.; Robey, R.W.; Belinsky, M.G.; Shchaveleva, I.; Ren, X.Q.; Sugimoto, Y.; Ross, D.D.; Bates, S.E.; Kruh, G.D. Transport of methotrexate, methotrexate polyglutamates, and 17beta-estradiol 17-(beta-D-glucuronide) by ABCG2: effects of acquired mutations at R482 on methotrexate transport. Cancer Res., 2003, 63(14), 4048-4054.
48. Krishnamurthy, P.; Schuetz, J.D. Role of ABCG2/BCRP in biology and medicine. Annu. Rev. Pharmacol. Toxicol., 2006, 46, 381-410.
49. Smith, J.M.; Prichard, R.K. Localization of p-glycoprotein mRNA in the tissues of Haemonchus contortus adult worms and its relative abundance in drug-selected and susceptible strains. J. Parasitol., 2002, 88(3), 612-620.
50. Nunes, F.; Wolf, M.; Hartmann, J.; Paul, R.J. The ABC transporter PGP-2 from Caenorhabditis elegans is expressed in the sensory neuron pair AWA and contributes to lysosome formation and lipid storage within the intestine. Biochem. Biophys. Res. Commun., 2005, 338(2), 862-871.
51. Lincke, C.R.; The, I.; van Groenigen, M.; Borst, P. The Pglycoprotein gene family of Caenorhabditis elegans. Cloning and characterization of genomic and complementary DNA sequences. J. Mol. Biol., 1992, 228(2), 701-711.
52. Xu, M.; Molento, M.; Blackhall, W.; Ribeiro, P.; Beech, R.; Prichard, R. Ivermectin resistance in nematodes may be caused by alteration of P-glycoprotein homolog. Mol. Biochem. Parasitol., 1998, 91(2), 327-335.
53. Jones, P.M.; George, A.M. Multidrug resistance in parasites: ABC transporters, P-glycoproteins and molecular modelling. Int. J. Parasitol., 2005, 35(5), 555-566.
54. James, C.E.; Davey, M.W. Increased expression of ABC transport proteins is associated with ivermectin resistance in the model nematode Caenorhabditis elegans. Int. J. Parasitol., 2009, 39(2), 213-220.
55. Prichard, R.K.; Roulet, A. ABC transporters and beta-tubulin in macrocyclic lactone resistance: prospects for marker development. Parasitology, 2007, 134, (Pt 8), 1123-1132.
56. Hochman, J.H.; Yamazaki, M.; Ohe, T.; Lin, J.H. Evaluation of drug interactions with P-glycoprotein in drug discovery: in vitro assessment of the potential for drug-drug interactions with Pglycoprotein. Curr. Drug Metab., 2002, 3(3), 257-273.
57. Garrigues, A.; Nugier, J.; Orlowski, S.; Ezan, E. A high-throughput screening microplate test for the interaction of drugs with P-glycoprotein. Anal. Biochem., 2002, 305(1), 106-114.
58. Hollo, Z.; Homolya, L.; Davis, C.W.; Sarkadi, B. Calcein accumulation as a fluorometric functional assay of the multidrug transporter. Biochim. Biophys. Acta, 1994, 1191(2), 384-388.
59. 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. Kinetics of vinblastine secretion and interaction with modulators. J. Biol. Chem., 1993, 268(20), 14991-14997.
60. Scala, S.; Akhmed, N.; Rao, U.S.; Paull, K.; Lan, L.B.; Dickstein, B.; Lee, J.S.; Elgemeie, G.H.; Stein, W.D.; Bates, S.E. P-glycoprotein substrates and antagonists cluster into two distinct groups. Mol. Pharmacol., 1997, 51(6), 1024-1033.
61. Polli, J.W.; Wring, S.A.; Humphreys, J.E.; Huang, L.; Morgan, J.B.; Webster, L.O.; Serabjit-Singh, C.S. Rational use of in vitro P-glycoprotein assays in drug discovery. J. Pharmacol. Exp. Ther., 2001, 299(2), 620-628.
62. Didier, A.; Loor, F. The abamectin derivative ivermectin is a potent P-glycoprotein inhibitor. Anticancer Drugs, 1996, 7(7), 745-751.
63. Eneroth, A.; Astrom, E.; Hoogstraate, J.; Schrenk, D.; Conrad, S.; Kauffmann, H.M.; Gjellan, K. Evaluation of a vincristine resistant Caco-2 cell line for use in a calcein AM extrusion screening assay for P-glycoprotein interaction. Eur. J. Pharm. Sci., 2001, 12(3), 205-214.
64. Schinkel, A.H.; Wagenaar, E.; Mol, C.A.; van Deemter, L. P-glycoprotein in the blood-brain barrier of mice influences the brain penetration and pharmacological activity of many drugs. J. Clin. Invest., 1996, 97(11), 2517-2524.
65. Twentyman, P.R. Cyclosporins as drug resistance modifiers. Biochem. Pharmacol., 1992, 43(1), 109-117.
66. Pouliot, J.F.; L'Heureux, F.; Liu, Z.; Prichard, R.K.; Georges, E. Reversal of P-glycoprotein-associated multidrug resistance by ivermectin. Biochem. Pharmacol., 1997, 53(1), 17-25.
67. Saeki, T.; Ueda, K.; Tanigawara, Y.; Hori, R.; Komano, T. Human P-glycoprotein transports cyclosporin A and FK506. J. Biol. Chem., 1993, 268(9), 6077-6080.
68. Nagy, H.; Goda, K.; Fenyvesi, F.; Bacso, Z.; Szilasi, M.; Kappelmayer, J.; Lustyik, G.; Cianfriglia, M.; Szabo, G., Jr. Distinct groups of multidrug resistance modulating agents are distinguished by competition of P-glycoprotein-specific antibodies. Biochem. Biophys. Res. Commun., 2004, 315(4), 942-949.
69. Garrigues, A.; Loiseau, N.; Delaforge, M.; Ferte, J.; Garrigos, M.; Andre, F.; Orlowski, S. Characterization of two pharmacophores on the multidrug transporter P-glycoprotein. Mol. Pharmacol., 2002, 62(6), 1288-1298.
70. Brayden, D.J.; Griffin, J. Avermectin transepithelial transport in MDR1- and MRP-transfected canine kidney monolayers. Vet. Res. Commun., 2008, 32(1), 93-106.
71. Griffin, J.; Fletcher, N.; Clemence, R.; Blanchflower, S.; Brayden, D.J. Selamectin is a potent substrate and inhibitor of human and canine P-glycoprotein. J. Vet. Pharmacol. Ther., 2005, 28(3), 257-265.
72. Vellarkad, N.; Viswanadhan, A.K.; Ghose, A.K.; Revankar, G.R.; Robins, R.K. Atomic physicochemical parameters for three dimensional structure directed quantitative structure-activity relationships. Additional parameters for hydrophobic and dispersive interactions and their application for an automated superposition of certain naturally occurring nucleoside antibiotics. J. Chem. Inf. Comp. Sci., 1989, 29163-172.
73. Lespine, A.; Dupuy, J.; Orlowski, S.; Nagy, T.; Glavinas, H.; Krajcsi, P.; Alvinerie, M. Interaction of ivermectin with multidrug resistance proteins (MRP1, 2 and 3). Chem. Biol. Interact., 2006, 159(3), 169-179.
74. Kwei, G.Y.; Alvaro, R.F.; Chen, Q.; Jenkins, H.J.; Hop, C.E.; Keohane, C.A.; Ly, V.T.; Strauss, J.R.; Wang, R.W.; Wang, Z.; Pippert, T.R.; Umbenhauer, D.R. Disposition of ivermectin and cyclosporin A in CF-1 mice deficient in mdr1a P-glycoprotein. Drug Metab. Dispos., 1999, 27(5), 581-587.
75. Mealey, K.L.; Bentjen, S.A.; Gay, J.M.; Cantor, G.H. Ivermectin sensitivity in collies is associated with a deletion mutation of the mdr1 gene. Pharmacogenetics, 2001, 11(8), 727-733.
76. Roulet, A.; Puel, O.; Gesta, S.; Lepage, J.F.; Drag, M.; Soll, M.; Alvinerie, M.; Pineau, T. MDR1-deficient genotype in Collie dogs hypersensitive to the P-glycoprotein substrate ivermectin. Eur. J. Pharmacol., 2003, 460(2-3), 85-91.
77. Nies, A.T.; Jedlitschky, G.; Konig, J.; Herold-Mende, C.; Steiner, H.H.; Schmitt, H.P.; Keppler, D. Expression and immunolocalization of the multidrug resistance proteins, MRP1-MRP6 (ABCC1-ABCC6), in human brain. Neuroscience, 2004, 129(2), 349-360.
78. Rao, V.V.; Dahlheimer, J.L.; Bardgett, M.E.; Snyder, A.Z.; Finch, R.A.; Sartorelli, A.C.; Piwnica-Worms, D. Choroid plexus epithelial expression of MDR1 P glycoprotein and multidrug resistance-associated protein contribute to the blood-cerebrospinal-fluid drug-permeability barrier. Proc. Natl. Acad. Sci. USA, 1999, 96(7), 3900-3905.
79. Cooray, H.C.; Blackmore, C.G.; Maskell, L.; Barrand, M.A. Localisation of breast cancer resistance protein in microvessel endothelium of human brain. Neuroreport, 2002, 13(16), 2059-2063.
80. Cisternino, S.; Mercier, C.; Bourasset, F.; Roux, F.; Scherrmann, J.M. Expression, up-regulation, and transport activity of the multidrug-resistance protein Abcg2 at the mouse blood-brain barrier. Cancer Res., 2004, 64(9), 3296-3301.
81. Laffont, C.M.; Toutain, P.L.; Alvinerie, M.; Bousquet-Melou, A. Intestinal secretion is a major route for parent ivermectin elimination in the rat. Drug Metab. Dispos., 2002, 30(6), 626-630.
82. Ballent, M.; Lifschitz, A.; Virkel, G.; Sallovitz, J.; Lanusse, C. Modulation of the P-glycoprotein-mediated intestinal secretion of ivermectin: in vitro and in vivo assessments. Drug Metab. Dispos., 2006, 34(3), 457-463.
83. Lifschitz, A.; Ballent, M.; Virkel, G.; Sallovitz, J.; Lanusse, C. Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation. J. Pharm. Pharmacol., 2006, 58(8), 1055-1062.
84. Stephens, R.H.; Tanianis-Hughes, J.; Higgs, N.B.; Humphrey, M.; Warhurst, G. Region-dependent modulation of intestinal permeability by drug efflux transporters: in vitro studies in mdr1a(-/-) mouse intestine. J. Pharmacol. Exp. Ther., 2002, 303(3), 1095-1101.
85. Takano, M.; Yumoto, R.; Murakami, T. Expression and function of efflux drug transporters in the intestine. Pharmacol. Ther., 2006, 109(1-2), 137-161.
86. Dupuy, J.; Larrieu, G.; Sutra, J.F.; Eeckhoutte, C.; Alvinerie, M. Influence of verapamil on the efflux and metabolism of 14C moxidectin in cultured rat hepatocytes. J. Vet. Pharmacol. Ther., 2001, 24(3), 171-177.
87. Dupuy, J.; Lespine, A.; Sutra, J.F.; Alvinerie, M. The interaction between moxidectin and MDR transporters in primary cultures of rat hepatocytes. J. Vet. Pharmacol. Ther., 2006, 29(2), 107-111.
88. Taipalensuu, J.; Tornblom, H.; Lindberg, G.; Einarsson, C.; Sjoqvist, F.; Melhus, H.; Garberg, P.; Sjostrom, B.; Lundgren, B.; Artursson, P. Correlation of gene expression of ten drug efflux proteins of the ATP-binding cassette transporter family in normal human jejunum and in human intestinal epithelial Caco-2 cell monolayers. J. Pharmacol. Exp. Ther., 2001, 299(1), 164-170.
89. Schaub, T.P.; Kartenbeck, J.; Konig, J.; Vogel, O.; Witzgall, R.; Kriz, W.; Keppler, D. Expression of the conjugate export pump encoded by the mrp2 gene in the apical membrane of kidney proximal tubules. J. Am. Soc. Nephrol., 1997, 8(8), 1213-1221.
90. Barrett, J. Cytochrome P450 in parasitic protozoa and helminths. Comp. Biochem. Physiol. C Pharmacol. Toxicol. Endocrinol., 1998, 121(1-3), 181-183.
91. Rohrer, S.P.; Birzin, E.T.; Eary, C.H.; Schaeffer, J.M.; Shoop, W.L. Ivermectin binding sites in sensitive and resistant Haemonchus contortus. J. Parasitol., 1994, 80(3), 493-497.
92. Sangster, N.C.; Bannan, S.C.; Weiss, A.S.; Nulf, S.C.; Klein, R.D.; Geary, T.G. Haemonchus contortus: sequence heterogeneity of internucleotide binding domains from P-glycoproteins. Exp. Parasitol., 1999, 91(3), 250-257.
93. Molento, M.B.; Prichard, R.K. Effects of the multidrug-resistance-reversing agents verapamil and CL 347,099 on the efficacy of ivermectin or moxidectin against unselected and drug-selected strains of Haemonchus contortus in jirds ( Meriones unguiculatus). Parasitol. Res., 1999, 85(12), 1007-1011.
94. Broeks, A.; Janssen, H.W.; Calafat, J.; Plasterk, R.H. A P-glycoprotein protects Caenorhabditis elegans against natural toxins. EMBO J., 1995, 14(9), 1858-1866.
95. Alvarez, A.I.; Merino, G.; Molina, A.J.; Pulido, M.M.; McKellar, Q.A.; Prieto, J.G. Role of ABC transporters in veterinary drug research and parasite resistance. Curr. Drug Deliv., 2006, 3(2), 199-206.
96. Ranjan, S.; Wang, G.T.; Hirschlein, C.; Simkins, K.L. Selection for resistance to macrocyclic lactones by Haemonchus contortus in sheep. Vet. Parasitol., 2002, 103(1-2), 109-117.
97. Tyrrell, K.L.; Dobson, R.J.; Stein, P.A.; Walkden-Brown, S.W. The effects of ivermectin and moxidectin on egg viability and larval development of ivermectin-resistant Haemonchus contortus. Vet. Parasitol., 2002, 107(1-2), 85-93.
98. Molento, M.B.; Wang, G.T.; Prichard, R.K. Decreased ivermectin and moxidectin sensitivity in Haemonchus contortus selected with moxidectin over 14 generations. Vet. Parasitol., 1999, 86(1), 77-81.
99. Laberge, R.M.; Karwatsky, J.; Lincoln, M.C.; Leimanis, M.L.; Georges, E. Modulation of GSH levels in ABCC1 expressing tumor cells triggers apoptosis through oxidative stress. Biochem. Pharmacol., 2007, 73(11), 1727-1737.
100. Merino, G.; Jonker, J.W.; Wagenaar, E.; Pulido, M.M.; Molina, A.J.; Alvarez, A.I.; Schinkel, A.H. Transport of anthelmintic benzimidazole drugs by breast cancer resistance protein (BCRP/ABCG2). Drug Metab. Dispos., 2005, 33(5), 614-618.
101. Dupuy, J.; Derlon, A.L.; Sutra, J.F.; Cadiergues, M.C.; Franc, M.; Alvinerie, M. Pharmacokinetics of selamectin in dogs after topical application. Vet. Res. Commun., 2004, 28(5), 407-413.
102. Vanapalli, S.R.; Hung, Y.P.; Fleckenstein, L.; Dzimianski, M.T.; McCall, J.W. Pharmacokinetics and dose proportionality of oral moxidectin in beagle dogs. Biopharm. Drug Dispos., 2002, 23(7), 263-272.
103. Kim, W.Y.; Benet, L.Z. P-glycoprotein (P-gp/MDR1)-mediated efflux of sex-steroid hormones and modulation of P-gp expression in vitro. Pharm. Res., 2004, 21(7), 1284-1293.
104. Kitagawa, S. Inhibitory effects of polyphenols on p-glycoprotein-mediated transport. Biol. Pharm. Bull., 2006, 29(1), 1-6.
105. Dupuy, J.; Larrieu, G.; Sutra, J.F.; Lespine, A.; Alvinerie, M. Enhancement of moxidectin bioavailability in lamb by a natural flavonoid: quercetin. Vet. Parasitol., 2003, 112(4), 337-347.
106. Garrigues, A.; Escargueil, A.E.; Orlowski, S. The multidrug transporter, P-glycoprotein, actively mediates cholesterol redistribution in the cell membrane. Proc. Natl. Acad. Sci. USA, 2002, 99(16), 10347-10352.
107. Eichelbaum, M.; Fromm, M.F.; Schwab, M. Clinical aspects of the MDR1 (ABCB1) gene polymorphism. Ther. Drug Monit., 2004, 26(2), 180-185.
108. Ameyaw, M.M.; Regateiro, F.; Li, T.; Liu, X.; Tariq, M.; Mobarek, A.; Thornton, N.; Folayan, G.O.; Githang'a, J.; Indalo, A.; Ofori-Adjei, D.; Price-Evans, D.A.; McLeod, H.L. MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics, 2001, 11(3), 217-221.
109. Morisaki, K.; Robey, R.W.; Ozvegy-Laczka, C.; Honjo, Y.; Polgar, O.; Steadman, K.; Sarkadi, B.; Bates, S.E. Single nucleotide polymorphisms modify the transporter activity of ABCG2. Cancer Chemother. Pharmacol., 2005, 56(2), 161-172.
110. Sparreboom, A.; Gelderblom, H.; Marsh, S.; Ahluwalia, R.; Obach, R.; Principe, P.; Twelves, C.; Verweij, J.; McLeod, H.L. Diflomotecan pharmacokinetics in relation to ABCG2 421C>A genotype. Clin. Pharmacol. Ther., 2004, 76(1), 38-44.
111. Yanase, K.; Tsukahara, S.; Mitsuhashi, J.; Sugimoto, Y. Functional SNPs of the breast cancer resistance protein-therapeutic effects and inhibitor development. Cancer Lett., 2006, 234(1), 73-80.
112. Olsen, H.G.; Nilsen, H.; Hayes, B.; Berg, P.R.; Svendsen, M.; Lien, S.; Meuwissen, T. Genetic support for a quantitative trait nucleotide in the ABCG2 gene affecting milk composition of dairy cattle. BMC Genet., 2007, 8(32), 1-9.
113. Lespine, A.; Alvinerie, M.; Vercruysse, J.; Prichard, R.K.; Geldhof, P. ABC transporter modulation: a strategy to enhance the activity of macrocyclic lactone anthelmintics. Trends Parasitol., 2008, 24(7), 293-298.
114. Alvinerie, M.; Dupuy, J.; Eeckhoutte, C.; Sutra, J.F. Enhanced absorption of pour-on ivermectin formulation in rats by co-administration of the multidrug-resistant-reversing agent verapamil. Parasitol. Res., 1999, 85(11), 920-922.
115. Lifschitz, A.; Virkel, G.; Sallovitz, J.; Imperiale, F.; Pis, A.; Lanusse, C. Loperamide-induced enhancement of moxidectin availability in cattle. J. Vet. Pharmacol. Ther., 2002, 25(2), 111-120.
116. Lifschitz, A.L.; Virkel, G.L.; Sallovitz, J.M.; Pis, A.; Imperiale, F.A.; Lanusse, C.E. Loperamide modifies the tissue disposition kinetics of ivermectin in rats. J. Pharm. Pharmacol., 2004, 56(1), 61-67.
117. Molento, M.B.; Lifschitz, A.; Sallovitz, J.; Lanusse, C.; Prichard, R. Influence of verapamil on the pharmacokinetics of the antiparasitic drugs ivermectin and moxidectin in sheep. Parasitol. Res., 2004, 92(2), 121-127.
118. Hugnet, C.; Lespine, A.; Alvinerie, M. Multiple oral dosing of ketoconazole increases dog exposure to ivermectin. J. Pharm. Pharm. Sci., 2007, 10(3), 311-318.
119. Alvinerie, M.; Dupuy, J.; Kiki-Mvouaka, S.; Sutra, J.F.; Lespine, A. Ketoconazole increases the plasma levels of ivermectin in sheep. Vet. Parasitol., 2008, 157(1-2), 117-122.
120. Ballent, M.; Lifschitz, A.; Virkel, G.; Sallovitz, J.; Lanusse, C. Involvement of P-glycoprotein on ivermectin kinetic behaviour in sheep: itraconazole-mediated changes on gastrointestinal disposition. J. Vet. Pharmacol. Ther., 2007, 30(3), 242-248.
121. Dupuy, J.; Lespine, A.; Sutra, J.F.; Alvinerie, M. Fumagillin, a new P-glycoprotein-interfering agent able to modulate moxidectin efflux in rat hepatocytes. J. Vet. Pharmacol. Ther., 2006, 29(6), 489-494.
122. Bartley, D.J.; Lespine, A.L.; Dupuy, J.; Alvinerie, M.; McAllister, H.; Gordon, Y.I.; Jackson, F. in The 21st International Conference of the World Association for the Advancement of Veterinary Parasitology; Vercruysse, J., Ed., 2007, p. 167
123. Lespine, A.; Bartley, D.J.; dupuy, J.; Alvinerie, M.; Jackson, F. in The 21st International Conference of the World Association for the Advancement of Veterinary Parasitology; Vercruysse, J., Ed., 2007, p. 396
124. Nobili, S.; Landini, I.; Giglioni, B.; Mini, E. Pharmacological strategies for overcoming multidrug resistance. Curr. Drug Targets, 2006, 7(7), 861-879.
125. Szakacs, G.; Paterson, J.K.; Ludwig, J.A.; Booth-Genthe, C.; Gottesman, M.M. Targeting multidrug resistance in cancer. Nat. Rev. Drug Discov., 2006, 5(3), 219-234.
126. Cornaire, G.; Woodley, J.; Hermann, P.; Cloarec, A.; Arellano, C.; Houin, G. Impact of excipients on the absorption of P-glycoprotein substrates in vitro and in vivo. Int. J. Pharm., 2004, 278(1), 119-131.
127. Batrakova, E.V.; Miller, D.W.; Li, S.; Alakhov, V.Y.; Kabanov, A.V.; Elmquist, W.F. Pluronic P85 enhances the delivery of digoxin to the brain: in vitro and in vivo studies. J. Pharmacol. Exp. Ther., 2001, 296(2), 551-557.
128. Seelig, A.; Gerebtzoff, G. Enhancement of drug absorption by noncharged detergents through membrane and P-glycoprotein binding. Expert Opin. Drug Metab. Toxicol., 2006, 2(5), 733-752.
129. Constantinides, P.P.; Wasan, K.M. Lipid formulation strategies for enhancing intestinal transport and absorption of P-glycoprotein (Pgp) substrate drugs: in vitro/in vivo case studies. J. Pharm. Sci., 2007, 96(2), 235-248.
130. Korystov, Y.N.; Ermakova, N.V.; Kublik, L.N.; Levitman, M.; Shaposhnikova, V.V.; Mosin, V.A.; Drinyaev, V.A.; Kruglyak, E.B.; Novik, T.S.; Sterlina, T.S. Avermectins inhibit multidrug resistance of tumor cells. Eur. J. Pharmacol., 2004, 493(1-3), 57-64.
131. Schinkel, A.H.; Jonker, J.W. Mammalian drug efflux transporters of the ATP binding cassette (ABC) family: an overview. Adv. Drug Deliv. Rev., 2003, 55(1), 3-29.
132. Breedveld, P.; Beijnen, J.H.; Schellens, J.H. Use of P-glycoprotein and BCRP inhibitors to improve oral bioavailability and CNS penetration of anticancer drugs. Trends Pharmacol. Sci., 2006, 27(1), 17-24.
133. Hermann, D.M.; Kilic, E.; Spudich, A.; Kramer, S.D.; Wunderli-Allenspach, H.; Bassetti, C.L. Role of drug efflux carriers in the healthy and diseased brain. Ann. Neurol., 2006, 60(5), 489-498.
134. Sasongko, L.; Link, J.M.; Muzi, M.; Mankoff, D.A.; Yang, X.; Collier, A.C.; Shoner, S.C.; Unadkat, J.D. Imaging P-glycoprotein transport activity at the human blood-brain barrier with positron emission tomography. Clin. Pharmacol. Ther., 2005, 77(6), 503-514.
135. Rengelshausen, J.; Goggelmann, C.; Burhenne, J.; Riedel, K.D.; Ludwig, J.; Weiss, J.; Mikus, G.; Walter-Sack, I.; Haefeli, W.E. Contribution of increased oral bioavailability and reduced non-glomerular renal clearance of digoxin to the digoxin-clarithromycin interaction. Br. J. Clin. Pharmacol., 2003, 56(1), 32-38.
136. Jonker, J.W.; Schinkel, A.H. Pharmacological and physiological functions of the polyspecific organic cation transporters: OCT1, 2, and 3 (SLC22A1-3). J. Pharmacol. Exp. Ther., 2004, 308(1), 2-9.
137. Hagenbuch, B.; Meier, P.J. Organic anion transporting polypeptides of the OATP/SLC21 family: phylogenetic classification as OATP/SLCO superfamily, new nomenclature and molecular/functional properties. Pflugers Arch., 2004, 447(5), 653-665.
138. Seithel, A.; Eberl, S.; Singer, K.; Auge, D.; Heinkele, G.; Wolf, N.B.; Dorje, F.; Fromm, M.F.; Konig, J. The influence of macrolide antibiotics on the uptake of organic anions and drugs mediated by OATP1B1 and OATP1B3. Drug Metab. Dispos., 2007, 35(5), 779-786.
139. Pan, G.; Elmquist, W.F. Mitoxantrone permeability in MDCKII cells is influenced by active influx transport. Mol. Pharm., 2007, 4(3), 475-483.
140. Porter, C.J.; Trevaskis, N.L.; Charman, W.N. Lipids and lipid-based formulations: optimizing the oral delivery of lipophilic drugs. Nat. Rev. Drug Discov., 2007, 6(3), 231-248.
141. Jaffrezou, J.P.; Laurent, G. The intriguing link between modulation of both multidrug resistance and ligand-toxin conjugate cytotoxicity. FEBS Lett., 1993, 323(3), 191-197.
142. Sehested, M.; Skovsgaard, T.; van Deurs, B.; Winther-Nielsen, H. Increase in nonspecific adsorptive endocytosis in anthracycline- and vinca alkaloid-resistant Ehrlich ascites tumor cell lines. J. Natl. Cancer Inst., 1987, 78(1), 171-179.
143. Field, F.J.; Born, E.; Chen, H.; Murthy, S.; Mathur, S.N. Esterification of plasma membrane cholesterol and triacylglycerol-rich lipoprotein secretion in CaCo-2 cells: possible role of p-glycoprotein. J. Lipid Res., 1995, 36(7), 1533-1543.
144. Debry, P.; Nash, E.A.; Neklason, D.W.; Metherall, J.E. Role of multidrug resistance P-glycoproteins in cholesterol esterification. J. Biol. Chem., 1997, 272(2), 1026-1031.
145. Orlowski, S.; Martin, S.; Escargueil, A. P-glycoprotein and 'lipid rafts': some ambiguous mutual relationships (floating on them, building them or meeting them by chance?). Cell Mol. Life Sci., 2006, 63(9), 1038-1059.
146. Tessner, T.G.; Stenson, W.F. Overexpression of MDR1 in an intestinal cell line results in increased cholesterol uptake from micelles. Biochem. Biophys. Res. Commun., 2000, 267(2), 565-571.
147. Issandou, M.; Grand-Perret, T. Multidrug resistance P-glycoprotein is not involved in cholesterol esterification. Biochem. Biophys. Res. Commun., 2000, 279(2), 369-377.
148. Luker, G.D.; Nilsson, K.R.; Covey, D.F.; Piwnica-Worms, D. Multidrug resistance (MDR1) P-glycoprotein enhances esterification of plasma membrane cholesterol. J. Biol. Chem., 1999, 274(11), 6979-6991.
149. Le Goff, W.; Settle, M.; Greene, D.J.; Morton, R.E.; Smith, J.D. Reevaluation of the role of the multidrug-resistant P-glycoprotein in cellular cholesterol homeostasis. J. Lipid Res., 2006, 47(1), 51-58.
150. Charman, W.N. Lipids, lipophilic drugs, and oral drug delivery-some emerging concepts. J. Pharm. Sci., 2000, 89(8), 967-978.
151. Smith, A.J.; van Helvoort, A.; van Meer, G.; Szabo, K.; Welker, E.; Szakacs, G.; Varadi, A.; Sarkadi, B.; Borst, P. MDR3 P-glycoprotein, a phosphatidylcholine translocase, transports several cytotoxic drugs and directly interacts with drugs as judged by interference with nucleotide trapping. J. Biol. Chem., 2000, 275(31), 23530-23539.
152. Velkov, T.; Chuang, S.; Wielens, J.; Sakellaris, H.; Charman, W.N.; Porter, C.J.; Scanlon, M.J. The interaction of lipophilic drugs with intestinal fatty acid-binding protein. J. Biol. Chem., 2005, 280(18), 17769-17776.
153. Yasuhisa, K.; Shin-ya, M.; Michinori, M.; Kazumitsu, U. Mechanism of multidrug recognition by MDR1/ABCB1. Cancer Sci., 2007, 98(9), 1303-1310.
154. Borst, P.; Zelcer, N.; van Helvoort, A. ABC transporters in lipid transport. Biochim. Biophys. Acta, 2000, 1486(1), 128-144.
155. Levy, E.; Spahis, S.; Sinnett, D.; Peretti, N.; Maupas-Schwalm, F.; Delvin, E.; Lambert, M.; Lavoie, M.A. Intestinal cholesterol transport proteins: an update and beyond. Curr. Opin. Lipidol., 2007, 18(3), 310-318.
156. van der Velde, A.E.; Vrins, C.L.; van den Oever, K.; Kunne, C.; Oude Elferink, R.P.; Kuipers, F.; Groen, A.K. Direct intestinal cholesterol
157. Stangl, H.; Hyatt, M.; Hobbs, H.H. Transport of lipids from high and low density lipoproteins via scavenger receptor-BI. J. Biol. Chem., 1999, 274(46), 32692-32698.
158. Acton, S.; Rigotti, A.; Landschulz, K.T.; Xu, S.; Hobbs, H.H.; Krieger, M. Identification of scavenger receptor SR-BI as a high density lipoprotein receptor. Science, 1996, 271(5248), 518-520.
159. Bietrix, F.; Yan, D.; Nauze, M.; Rolland, C.; Bertrand-Michel, J.; Comera, C.; Schaak, S.; Barbaras, R.; Groen, A.K.; Perret, B.; Terce, F.; Collet, X. Accelerated lipid absorption in mice overexpressing intestinal SR-BI. J. Biol. Chem., 2006, 281(11), 7214-7219.
160. Reboul, E.; Klein, A.; Bietrix, F.; Gleize, B.; Malezet-Desmoulins, C.; Schneider, M.; Margotat, A.; Lagrost, L.; Collet, X.; Borel, P. Scavenger receptor class B type I (SR-BI) is involved in vitamin E transport across the enterocyte. J. Biol. Chem., 2006, 281(8), 4739-4745.
161. Kapadia, S.B.; Barth, H.; Baumert, T.; McKeating, J.A.; Chisari, F.V. Initiation of hepatitis C virus infection is dependent on cholesterol and cooperativity between CD81 and scavenger receptor B type I. J. Virol., 2007, 81(1), 374-383.
162. Scarselli, E.; Ansuini, H.; Cerino, R.; Roccasecca, R.M.; Acali, S.; Filocamo, G.; Traboni, C.; Nicosia, A.; Cortese, R.; Vitelli, A. The human scavenger receptor class B type I is a novel candidate receptor for the hepatitis C virus. EMBO J., 2002, 21(19), 5017-5025.
163. Diaz, O.; Delers, F.; Maynard, M.; Demignot, S.; Zoulim, F.; Chambaz, J.; Trepo, C.; Lotteau, V.; Andre, P. Preferential association of Hepatitis C virus with apolipoprotein B48-containing lipoproteins. J. Gen. Virol., 2006, 87(Pt 10), 2983-2991.
164. Davies, J.P.; Chen, F.W.; Ioannou, Y.A. Transmembrane molecular pump activity of Niemann-Pick C1 protein. Science, 2000, 290(5500), 2295-2298.
165. Liscovitch, M.; Lavie, Y. Multidrug resistance: a role for cholesterol efflux pathways? Trends Biochem. Sci., 2000, 25(11), 530-534.
166. Underwood, K.W.; Andemariam, B.; McWilliams, G.L.; Liscum, L. Quantitative analysis of hydrophobic amine inhibition of intracellular cholesterol transport. J. Lipid Res., 1996, 37(7), 1556-1568.
167. Lange, Y.; Ye, J.; Steck, T.L. Circulation of cholesterol between lysosomes and the plasma membrane. J. Biol. Chem., 1998, 273(30), 18915-18922.
168. Fleisher, D.; Li, C.; Zhou, Y.; Pao, L.H.; Karim, A. Drug, meal and formulation interactions influencing drug absorption after oral administration. Clinical implications. Clin. Pharmacokinet., 1999, 36(3), 233-254.
169. Schuetz, E.; Strom, S. Promiscuous regulator of xenobiotic removal. Nat. Med., 2001, 7(5), 536-537.