Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs

Journal of Pharmacology and Experimental Therapeutics

Volumn 303, Issue 3, 2002, Pages 1029-1037

  Mahar Doan, Kelly M ^a   Humphreys, Joan E ^a   Webster, Lindsey O ^a   Wring, Stephen A ^a   Shampine, Larry J ^a   Serabjit Singh, Cosette J ^a   Adkison, Kimberly K ^a   Polli, Joseph W ^a  

^a GLAXOSMITHKLINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMANTADINE; AMITRIPTYLINE; BIPERIDEN; BROMOCRIPTINE; BUSPIRONE; CALCEIN; CARBAMAZEPINE; CENTRAL NERVOUS SYSTEM AGENTS; CHLORPROMAZINE; CHLORPROTHIXENE; CLOMIPRAMINE; DESIPRAMINE; DOXEPIN; FLUMAZENIL; FLUOXETINE; FLURAZEPAM; GLYCOPROTEIN P; IMIPRAMINE; KETAMINE; MEPROBAMATE; NALOXONE; NALTREXONE; NITRAZEPAM; NORDAZEPAM; SCOPOLAMINE; SELEGILINE; SUMATRIPTAN; TACRINE; UNINDEXED DRUG; ZIMELDINE;

ANIMAL CELL; ARTICLE; CENTRAL NERVOUS SYSTEM; CONTROLLED STUDY; DRUG MARKETING; DRUG PENETRATION; DRUG TRANSPORT; HYDROGEN BOND; LIPOPHILICITY; MEMBRANE PERMEABILITY; NONHUMAN; PRIORITY JOURNAL; SURFACE PROPERTY;

ANIMALS; BLOOD-BRAIN BARRIER; CELL LINE; CELL MEMBRANE PERMEABILITY; CENTRAL NERVOUS SYSTEM AGENTS; DOGS; DRUG DELIVERY SYSTEMS; P-GLYCOPROTEIN; PERMEABILITY; PHARMACEUTICAL PREPARATIONS;

EID: 0036896304     PISSN: 00223565     EISSN: None     Source Type: Journal    
DOI: 10.1124/jpet.102.039255     Document Type: Article

References (28)

1. Abbott NJ and Romero IA (1996) Transporting therapeutics across the blood-brain barrier. Mol Med Today 2:106-113.
2. Ajay, Bemis GW, and Murcko MA (1999) Designing libraries with CNS activity. J Med Chem 42:4942-4951.
3. Basak SC, Gute BD, and Drewes LR (1996) Predicting blood-brain transport of drugs: A computational approach. Pharm Res (NY) 13:775-778.
4. Clark DE (1999) Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 1. Prediction of intestinal absorption. J Pharm Sci 88:807-814.
5. Clark DE (2001) Prediction of intestinal absorption and blood-brain barrier penetration by computational methods. Comb Conib Chem High Throughput Screen 4:477-496.
6. Eytan GD, Regev R, Oren G, and Assaraf YG (1996) The role of passive transbilayer drug movement in multidrug resistance and its modulation. J Biol Chem 271:12897-12902.
7. Fischer H, Gottschlich R, and Seelig A (1998) Blood-brain barrier permeation: Molecular parameters governing passive diffusion. J Membr Biol 165:201-211.
8. Garberg P (1998) In vitro models of the blood-brain barrier. Altern Lab Anim 26:821-847.
9. Gilman AG, Rall TW, Nies AS, and Taylor P (1993) Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th Ed, McGraw-Hill, New York.
10. Goadsby PJ (2000) The pharmacology of headache. Prog Neurobiol 62:505-525.
11. Kusuhara H and Sugiyama Y (2001a) Efflux transport systems for drugs at the blood-brain barrier and blood-cerebrospinal fluid barrier (Part 1). Drug Discov Today 6:150-156.
12. Kusuhara H and Sugiyama Y (2001b) Efflux transport systems for drugs at the blood-brain barrier and blood-cerebrospinal fluid barrier (Part 2). Drug Discov Today 6:206-212.
13. Lipinski CA (2000) Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods 44:235-249.
14. O'Neil MJ, Smith A, and Heckelman PE, eds (2001) The Merck Index, 13th ed, Merck & Co., Whitehouse Station, NJ.
15. Pardridge WM (1997) Drug delivery to the brain. J Cereb Blood Flow Metab 17:713-731.
16. Pauli-Magnus C, von Richter O, Burk O, Ziegler A, Mettang T, Eichelbaum M, and Fromm MF (2000) Characterization of the major metabolites of verapamil as substrates and inhibitors of P-glycoprotein. J Pharmacol Exp Ther 293:376-382.
17. Platts JA, Butina D, Abraham MH, and Hersey A (1999) Estimation of molecular linear free energy relation descriptors using a group contribution approach. J Chem Inf Comput Sci 39:835-845.
18. Polli JW, Gombar V, Luscombe C, Wring SA, Humphreys JE, Morgan JB, Modi S, Hersey A, Read KD, Bertolotti L, et al. (2001a) Development and application of P-glycoprotein computational models in drug discovery and development. AAPS Pharmsci 3:R5096.
19. Polli JW, Humphreys JE, Wring SA, Burnette TC, Read KC, Hersey A, Butina D, Bertolotti L, Pugnaghi P, and Serabjit-Singh CJ (2000) Comparison of MDCK and bovine brain endothelial cells (BBECs) as a blood-brain barrier screen in early drug discovery, in Progress in the Reduction, Refinement and Replacement of Animal Experimentation (Balls M, van Zeller A-M, and Halder M, eds), pp 271-289, Elsevier Science, New York.
20. Polli JW, Jarrett JL, Studenberg SD, Humphreys JE, Dennis SW, Brouwer KR, and Woolley JL (1999) Role of P-glycoprotein on the CNS disposition of amprenavir (141W94), an HIV protease inhibitor. Pharm Res (NY) 16:1206-1212.
21. Polli JW, Wring SA, Humphreys JE, Huang L, Morgan JB, Webster LO, and Serabjit-Singh CJ (2001b) Rational use of in vitro P-glycoprotein assays in drug discovery. J Pharmacol Exp Ther 299:620-628.
22. Rubin LL and Staddon JM (1999) The cell biology of the blood-brain barrier. Annu Rev Neurosci 22:11-28.
23. Sawada GA, Barsuhn CL, Lutzke BS, Houghton ME, Padbury GE, Ho NFH, and Raub TJ (1999a) Increased lipophilicity and subsequent cell partitioning decrease passive transcellular diffusion of novel, highly lipophilic antioxidants. J Pharmacol Exp Ther 288:1317-1326.
24. Sawada GA, Williams LR, Lutzke BS, and Raub TJ (1999b) Novel, highly lipophilic antioxidants readily diffuse across the blood-brain barrier and access intracellular sites. J Pharmacol Exp Ther 288:1327-1333.
25. Schinkel AH (1999) P-glycoprotein, a gatekeeper in the blood-brain barrier. Adv Drug Delivery Rev 36:179-194.
26. van de Waterbeemd H, Camenisch G, Folkers G, Cheretien JR, and Raevsky OA (1998) Estimation of blood-brain barrier crossing of drugs using molecular size and shape and H-bonding descriptors. J Drug Targeting 6:151-165.
27. Veronesi B (1996) Characterization of the MDCK cell line for screening neurotoxicants. Neurotoxicology (Little Rock) 17:433-443.
28. Wring SA, Birkemo LS, Polli JW, Morgan DG, Morgan JB, Frick LW, and Serabjit-Singh CJ (2000) Automated dual LC/MS/MS with cassette analysis markedly increases throughput and accelerates drug discovery, in Proceedings of the 48th ASMS Conference on Mass Spectrometry and Allied Topics, June 11-15, 2000, Long Beach, CA, pp 779-780.