P-glycoprotein-based loperamide-cyclosporine drug interaction at the rat blood-brain barrier: Prediction from in vitro studies and extrapolation to humans

Molecular Pharmaceutics

Volumn 9, Issue 3, 2012, Pages 629-633

  Hsiao, Peng ^a   Unadkat, Jashvant D ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

Author keywords

blood brain barrier; cyclosporin A; drug drug interaction; in vitro to in vivo correlation; loperamide; N desmethyl loperamide; P glycoprotein

Indexed keywords

CARBON 11; CYCLOSPORIN A; DRUG METABOLITE; GLYCOPROTEIN P; LOPERAMIDE; N NORLOPERAMIDE; SANDIMUNE; UNCLASSIFIED DRUG; VERAPAMIL;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BLOOD BRAIN BARRIER; CALCULATION; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG DISTRIBUTION; IN VITRO STUDY; ISOTOPE LABELING; MALE; NONHUMAN; PREDICTION; PRIORITY JOURNAL; RAT;

ANIMALS; BLOOD-BRAIN BARRIER; CYCLOSPORINE; DRUG INTERACTIONS; HUMANS; LOPERAMIDE; MALE; P-GLYCOPROTEIN; RATS; RATS, SPRAGUE-DAWLEY;

EID: 84858047915     PISSN: 15438384     EISSN: 15438392     Source Type: Journal    
DOI: 10.1021/mp200563a     Document Type: Article

References (26)

1. Passchier, J.; Comley, R.; Salinas, C.; Rabiner, E.; Gunn, R.; Cunningham, V.; Wilson, A.; Houle, S.; Gee, A.; Laruelle, M. Blood brain barrier permeability of [11C]loperamide in humans under normal and impaired P-glycoprotein function J. Nucl. Med. 2008, 49 (Suppl. 1) 211P
2. Eyal, S.; Hsiao, P.; Unadkat, J. D. Drug interactions at the blood-brain barrier: fact or fantasy? Pharmacol. Ther. 2009, 123, 80-104
3. 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, 2517-24 (Pubitemid 26187339)
4. Hendrikse, N. H.; Schinkel, A. H.; de Vries, E. G.; Fluks, E.; Van der Graaf, W. T.; Willemsen, A. T.; Vaalburg, W.; Franssen, E. J. Complete in vivo reversal of P-glycoprotein pump function in the blood-brain barrier visualized with positron emission tomography Br. J. Pharmacol. 1998, 124, 1413-8 (Pubitemid 28360563)
5. Kim, R. B.; Fromm, M. F.; Wandel, C.; Leake, B.; Wood, A. J.; Roden, D. M.; Wilkinson, G. R. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors J. Clin. Invest. 1998, 101, 289-94 (Pubitemid 28067324)
6. Choo, E. F.; Kurnik, D.; Muszkat, M.; Ohkubo, T.; Shay, S. D.; Higginbotham, J. N.; Glaeser, H.; Kim, R. B.; Wood, A. J.; Wilkinson, G. R. Differential in vivo sensitivity to inhibition of P-glycoprotein located in lymphocytes, testes, and the blood-brain barrier J. Pharmacol. Exp. Ther. 2006, 317, 1012-8 (Pubitemid 43764103)
7. Choo, E. F.; Leake, B.; Wandel, C.; Imamura, H.; Wood, A. J.; Wilkinson, G. R.; Kim, R. B. Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes Drug Metab. Dispos. 2000, 28, 655-60 (Pubitemid 30390404)
8. Hsiao, P.; Sasongko, L.; Link, J. M.; Mankoff, D. A.; Muzi, M.; Collier, A. C.; Unadkat, J. D. Verapamil P-glycoprotein transport across the rat blood-brain barrier: cyclosporine, a concentration inhibition analysis, and comparison with human data J. Pharmacol. Exp. Ther. 2006, 317, 704-10
9. 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, 503-14 (Pubitemid 40824964)
10. Aller, S. G.; Yu, J.; Ward, A.; Weng, Y.; Chittaboina, S.; Zhuo, R.; Harrell, P. M.; Trinh, Y. T.; Zhang, Q.; Urbatsch, I. L.; Chang, G. Structure of P-glycoprotein reveals a molecular basis for poly-specific drug binding Science 2009, 323, 1718-22
11. Martin, C.; Berridge, G.; Higgins, C. F.; Mistry, P.; Charlton, P.; Callaghan, R. Communication between multiple drug binding sites on P-glycoprotein Mol. Pharmacol. 2000, 58, 624-32
12. Martin, C.; Berridge, G.; Mistry, P.; Higgins, C.; Charlton, P.; Callaghan, R. The molecular interaction of the high affinity reversal agent XR9576 with P-glycoprotein Br. J. Pharmacol. 1999, 128, 403-11 (Pubitemid 29458600)
13. Martin, C.; Berridge, G.; Mistry, P.; Higgins, C.; Charlton, P.; Callaghan, R. Drug binding sites on P-glycoprotein are altered by ATP binding prior to nucleotide hydrolysis Biochemistry 2000, 39, 11901-6
14. Shapiro, A. B.; Fox, K.; Lam, P.; Ling, V. Stimulation of P-glycoprotein-mediated drug transport by prazosin and progesterone. Evidence for a third drug-binding site Eur. J. Biochem. 1999, 259, 841-50 (Pubitemid 29075514)
15. Taub, M. E.; Podila, L.; Ely, D.; Almeida, I. Functional assessment of multiple P-glycoprotein (P-gp) probe substrates: influence of cell line and modulator concentration on P-gp activity Drug Metab. Dispos. 2005, 33, 1679-87 (Pubitemid 41539967)
16. Miyazaki, H.; Nambu, K.; Matsunaga, Y.; Hashimoto, M. Disposition and metabolism of [14C]loperamide in rats Eur. J. Drug Metab. Pharmacokinet. 1979, 4, 199-206
17. Heykants, J.; Michiels, M.; Knaeps, A.; Brugmans, J. Loperamide (R 18 553), a novel type of antidiarrheal agent. Part 5: the pharmacokinetics of loperamide in rats and man Arzneim. Forsch. 1974, 24, 1649-53
18. Kamali, F.; Adriaens, L.; Huang, M. L.; Woestenborghs, R.; Emanuel, M.; Rawlins, M. D. Dose proportionality study of loperamide following oral administration of loperamide oxide Eur. J. Clin. Pharmacol. 1992, 42, 693-4
19. Zoghbi, S. S.; Liow, J. S.; Yasuno, F.; Hong, J.; Tuan, E.; Lazarova, N.; Gladding, R. L.; Pike, V. W.; Innis, R. B. 11C-loperamide and its N-desmethyl radiometabolite are avid substrates for brain permeability-glycoprotein efflux J. Nucl. Med. 2008, 49, 649-56 (Pubitemid 351520614)
20. Lazarova, N.; Zoghbi, S. S.; Hong, J.; Seneca, N.; Tuan, E.; Gladding, R. L.; Liow, J. S.; Taku, A.; Innis, R. B.; Pike, V. W. Synthesis and evaluation of [N-methyl-11C]N-desmethyl-loperamide as a new and improved PET radiotracer for imaging P-gp function J. Med. Chem. 2008, 51, 6034-43
21. Yoshida, K.; Nambu, K.; Arakawa, S.; Miyazaki, H.; Hashimoto, M. Metabolites of loperamide in rats Biomed. Mass Spectrom. 1979, 6, 253-9 (Pubitemid 9233743)
22. Vandenbossche, J.; Huisman, M.; Xu, Y.; Sanderson-Bongiovanni, D.; Soons, P. Loperamide and P-glycoprotein inhibition: assessment of the clinical relevance J. Pharm. Pharmacol. 2010, 62, 401-12
23. Zolnerciks, J. K.; Booth-Genthe, C. L.; Gupta, A.; Harris, J.; Unadkat, J. D. Substrate- and species-dependent inhibition of p-glycoprotein-mediated transport: Implications for predicting in vivo drug interactions J. Pharm. Sci. 2011, 100 (8) 3055-61
24. Moerman, L.; Wyffels, L.; Slaets, D.; Raedt, R.; Boon, P.; De Vos, F. Antiepileptic drugs modulate P-glycoproteins in the brain: A mice study with (11)C-desmethylloperamide Epilepsy Res. 2011, 94, 18-25
25. Corkill, G.; Turner, D.; Pufong, B.; Gill, H.; Fessey, R.; Dilworth, C. In vitro evaluation of P-glycoprotein inhibition using loperamide as a probe substrate. 10th European ISSX Meeting. 2008.
26. Hsiao, P.; Bui, T.; Ho, R. J.; Unadkat, J. D. In vitro-to-in vivo prediction of P-glycoprotein-based drug interactions at the human and rodent blood-brain barrier Drug Metab. Dispos. 2008, 36, 481-4 (Pubitemid 351397990)