Influence of nonspecific brain and plasma binding on CNS exposure: Implications for rational drug discovery

Biopharmaceutics and Drug Disposition

Volumn 23, Issue 8, 2002, Pages 327-338

  Kalvass, J Cory ^a   Maurer, Tristan S ^a  

^a PFIZER INC   (United States)

Author keywords

CNS; Discovery; Efflux; Nonspecific binding; P glycoprotein

Indexed keywords

DRUG CARRIER; GLYCOPROTEIN P; NEW DRUG;

ACTIVE TRANSPORT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD BRAIN BARRIER; BRAIN; CELL STRAIN CACO 2; CEREBROSPINAL FLUID; CONTROLLED STUDY; DOSE RESPONSE; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DELIVERY SYSTEM; DRUG DESIGN; DRUG EFFECT; DRUG EXPOSURE; DRUG TARGETING; DRUG TISSUE LEVEL; FRACTIONATION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; INTERMETHOD COMPARISON; MOUSE; NONHUMAN; PREDICTION; QUANTITATIVE ANALYSIS; RAT;

ANIMALS; ATP-BINDING CASSETTE TRANSPORTERS; BRAIN; MICE; MICE, KNOCKOUT; P-GLYCOPROTEINS; PHARMACEUTICAL PREPARATIONS; PROTEIN BINDING; RATS; RATS, SPRAGUE-DAWLEY; TECHNOLOGY, PHARMACEUTICAL;

EID: 0036874825     PISSN: 01422782     EISSN: None     Source Type: Journal    
DOI: 10.1002/bdd.325     Document Type: Article

References (35)

1. Wagner JG, Northam JI, Alway CD, Carpenter OS. Blood levels of drug at the equilibrium state after multiple dosing. Nature 1965; 207: 1301-1302.
2. Takasato Y, Rapoport SI, Smith QR. An in situ brain perfusion technique to study cerebrovascular transport in the rat. Am J Physiol 1984; 247: H484-H493.
3. Collins JM, Dedrick RL. Distributed model for drug delivery to CSF and brain tissue. Am J Physiol 1983; 245: R303-R310.
4. Kakee A, Terasaki T, Sugiyama Y. Brain efflux index as a novel method of analyzing efflux transport at the blood-brain barrier. J Pharmacol Exp Ther 1996; 277: 1550-1559.
5. Garberg P. In vitro models of the blood-brain barrier. ATLA 1998; 26: 821-847.
6. Dagenais C, Rousselle C, Pollack GM, Scherrmann JM. Development of an in situ mouse brain perfusion model and its application to mdr1a P-glycoprotein-deficient mice. J Cereb Blood Flow Metab 2000; 20: 381-386.
7. Young RC, Mitchell RC, Brown TH, et al. Development of a new physicochemical model for brain penetration and its application to the design of centrally acting H2 receptor histamine antagonists. J Med Chem 1988; 31: 656-671.
8. Abraham MH, Chadha HS, Mitchell RC. Hydrogen bonding. 33. Factors that influence the distribution of solutes between blood and brain. J Pharm Sci 1994; 83: 1257-1268.
9. Clark DE. Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 2. Prediction of blood-brain barrier penetration. J Pharm Sci 1999; 88: 815-821.
10. Lombardo F, Blake JF, Curatolo WJ. Computation of brain-blood partitioning of organic solutes via free energy calculations. J Med Chem 1996; 39: 4750-4755.
11. Rowland M. Physiologic pharmacokinetic models and interanimal species scaling. Pharmacol Ther 1985; 29: 49-68.
12. Wilkinson GR, Shand DG. Commentary: a physiological approach to hepatic drug clearance. Clin Pharmacol Ther 1975; 18: 377-390.
13. Gillette JR. Factors affecting drug metabolism. Ann NY Acad Sci 1971; 179: 43-66.
14. van de Waterbeemd H, Smith DA, Jones BC. Lipophilicity in PK design: methyl, ethyl, futile. J Comput Aid Mol Design 2001; 15: 273-286.
15. van De Waterbeemd H, Smith DA, Beaumont K, Walker DK. Property-based design: optimization of drug absorption and pharmacokinetics. J Med Chem 2001; 44: 1313-1333.
16. Schinkel AH, Smit JJ, van Tellingen O, et al. 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: 491-502.
17. Schinkel AH, Wagenaar E, Mol CA, 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: 2517-2524.
18. Matheny CJ, Lamb MW, Brouwer KR, Pollack GM. Pharmacokinetic and pharmacodynamic implications of P-glycoprotein modulation. Pharmacotherapy 2001; 21: 778-796.
19. Schinkel AH, Mayer U, Wagenaar E, et al. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc Natl Acad Sci USA 1997; 94: 4028-4033.
20. van Asperen J, van Tellingen O, Schinkel AH, Beijnen JH. Comparative pharmacokinetics of vinblastine after a 96-hour continuous infusion in wild-type mice and mice lacking mdr1a P-glycoprotein. J Pharmacol Exp Ther 1999; 289: 329-333.
21. Uhr M, Steckler T, Yassouridis A, Holsboer F. Penetration of amitriptyline, but not of fluoxetine, into brain is enhanced in mice with blood-brain barrier deficiency due to mdr1a P-glycoprotein gene disruption. Neuropsychopharmacology 2000; 22: 380-387.
22. Kim RB, Fromm MF, Wandel C, et al. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 1998; 101: 289-294.
23. Kawahara M, Sakata A, Miyashita T, Tamai I, Tsuji A. Physiologically based pharmacokinetics of digoxin in mdr1a knockout mice. J Pharm Sci 1999; 88: 1281-1287.
24. Smith BJ, Doran AC, McLean S, Tingley FD, 3rd, O'Neill BT, Kajiji SM. P-glycoprotein efflux at the blood-brain barrier mediates differences in brain disposition and pharmacodynamics between two structurally related neurokinin-1 receptor antagonists. J Pharmacol Exp Ther 2001; 298: 1252-1259.
25. Clausen J, Bickel MH. Prediction of drug distribution in distribution dialysis and in vivo from binding to tissues and blood. J Pharm Sci 1993; 82: 345-349.
26. Lin JH, Sugiyama Y, Awazu S, Hanano M. In vitro and in vivo evaluation of the tissue-to-blood partition coefficient for physiological pharmacokinetic models. J Pharmacokinet Biopharm 1982; 10: 637-647.
27. Harashima H, Sugiyama Y, Sawada Y, Iga T, Hanano M. Comparison between in-vivo and in-vitro tissue-to-plasma unbound concentration ratios (Kp,f) of quinidine in rats. J Pharm Pharmacol 1984; 36: 340-342.
28. Schuhmann G, Fichtl B, Kurz H. Prediction of drug distribution in vivo on the basis of in vitro binding data. Biopharm Drug Dispos 1987; 8: 73-86.
29. Fichtl B, v. Nieciecki A, Walter K. Tissue binding versus plasma binding of drugs: general principles and pharmacokinetic consequences. Adv Drug Res 1991; 20: 117-166.
30. Yee, S. In vitro permeability across Caco-2 cells (colonic) can predict in vivo (small intestinal) absorption in man - fact or myth. Pharm Res 1997; 14: 763-766.
31. Romer J, Bickel MH. A method to estimate binding constants at variable protein concentrations. J Pharm Pharmacol 1979; 31: 7-11.
32. Kurz H, Fichtl B. Binding of drugs to tissues. Drug Metab Rev 1983; 14: 467-510.
33. Ooie T, Terasaki T, Suzuki H, Sugiyama Y. Quantitative brain microdialysis study on the mechanism of quinolones distribution in the central nervous system. Drug Metab Dispos 1997; 25: 784-789.
34. Takasawa K, Terasaki T, Suzuki H, Ooie T, Sugiyama Y. Distributed model analysis of 3′-azido-3′-deoxythymidine and 2′,3′-dideoxyinosine distribution in brain tissue and cerebrospinal fluid. J Pharmacol Exp Ther 1997; 282: 1509-1517.
35. Ooie T, Terasaki T, Suzuki H, Sugiyama Y. Kinetic evidence for active efflux transport across the blood-brain barrier of quinolone antibiotics. J Pharmacol Exp Ther 1997; 283: 293-304.