Role of efflux transport across the blood-brain barrier and blood- cerebrospinal fluid barrier on the disposition of xenobiotics in the central nervous system

Advanced Drug Delivery Reviews

Volumn 25, Issue 2-3, 1997, Pages 257-285

  Suzuki, Hiroshi ^a   Terasaki, Tetsuya ^a,b   Sugiyama, Yuichi ^a  

^a UNIVERSITY OF TOKYO   (Japan)

^b TOHOKU UNIVERSITY   (Japan)

Author keywords

Blood brain barrier; Blood cerebrospinal fluid barrier; Cerebrospinal fluid; Choroid plexus; Organic anions; Organic cations; Transport

Indexed keywords

ANTIBIOTICS; BLOOD; BODY FLUIDS; BRAIN; DRUG PRODUCTS; IONIC DRUGS; NEUROLOGY; PHARMACOKINETICS;

BLOOD BRAIN BARRIER; BLOOD CEREBROSPINAL FLUID BARRIER; CEREBROSPINAL FLUID; CHOROID PLEXUS; ORGANIC ANIONS; ORGANIC CATIONS; XENOBIOTICS;

DRUG THERAPY;

CEFODIZIME; CEFTRIAXONE; CHOLINE DERIVATIVE; CILASTATIN; CIMETIDINE; CREATININE; HISTAMINE AGONIST; IMIPENEM; PENICILLIN G; PROBENECID; PROCAINAMIDE; QUINIDINE; QUININE; SALICYLIC ACID; XENOBIOTIC AGENT;

ARTICLE; BLOOD BRAIN BARRIER; BLOOD CEREBROSPINAL FLUID BARRIER; CALCULATION; CENTRAL NERVOUS SYSTEM; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG CEREBROSPINAL FLUID LEVEL; DRUG DISPOSITION; DRUG ELIMINATION; DRUG PENETRATION; DRUG TRANSPORT; HUMAN; INTRACEREBROVENTRICULAR DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; MEMBRANE TRANSPORT; NONHUMAN; PRIORITY JOURNAL;

EID: 0343554785     PISSN: 0169409X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0169-409X(97)00503-6     Document Type: Review

References (159)

1. Rapoport, S.I. (1976) Blood-brain barrier in physiology and medicine. Raven, New York.
2. Bradbury, M.W. (1979) The concept of a blood-brain barrier. Wiley, Chichester.
3. Davson, H. (1989) History of the blood-brain barrier concept In: E. A. Neuwelt (Ed.), Implications of the blood-brain barrier and its manipulation. Plenum, New York, pp. 27-52.
4. Brightman, M.W. (1989) The anatomic basis of the blood-brain barrier. In: E.A. Neuwelt (Ed.), Implications of the blood-brain barrier and its manipulation. Plenum, New York, pp. 53-84.
5. Pardridge, W.M. (1991) Peptide drug delivery to the brain. Raven, New York.
6. Pardridge, W.M. (1995) Vector-mediated peptide drug delivery to the brain. Adv. Drug Deliv. Rev. 15, 109-146.
7. Pardridge, W.M. (1995) Transport of small molecules through the blood-brain barrier: biology and methodology. Adv. Drug Deliv. Rev. 15, 5-36.
8. Tsuji, A. and Tamai, I. (1997) Blood-brain barrier function of P-glycoprotein. Adv. Drug. Deliv. Rev. 25, 287-298.
9. Bradbury, M.W. (1989) Transport across the blood-brain barrier. In: E.A. Neuwelt (Ed.), Implications of the blood-brain barrier and its manipulation. Plenum, New York, pp. 119-136.
10. Fenstermacher, J.D. (1989) Pharmacology of the blood-brain barrier. In: E.A. Neuwelt (Ed.), Implications of the blood-brain barrier and its manipulation. Plenum, New York, pp. 137-156.
11. Fenstermacher, J.D., Blasberg, R.G. and Patlak, C.S. (1981) Methods for quantifying the transport of drugs across the brain barrier systems. Pharmacol. Ther. 14, 217-248.
12. Fenstermacher, J.D. and Rapoport, S.I. (1984) Blood-brain barrier. In: E.M. Renkin and C.C. Michel (Ed.), Handbook of physiology, Section 2: The cerebrovascular system, Vol. IV: Microcirculation, American Physiological Society, Bethesda, MD, pp. 969-1000.
13. Smith, Q.R. (1989) Quantification of blood-brain barrier permeability. In: E.A. Neuwelt (Ed.), Implications of the blood-brain barrier and its manipulation. Plenum, New York, pp. 85-118.
14. Cserr, H.F. (1971) Physiology of the choroid plexus. Physiol. Rev. 51, 273-311.
15. Woodbury, D.M., Johanson, C.E. and Brondsted, H. (1974) Maturation of the blood-brain and blood-CSF barriers and transport systems. In: E. Zimmermann and R. George (Eds.), Narcotics and the hypothalamus. Raven. New York, pp. 225-247.
16. Johanson, C.E. (1988) The choroid plexus-arachnoid membrane-cerebrospinal fluid system. In: A.A. Boulton, G.B. Baker and W. Walz (Eds.), Neuromethods: The Neuronal Microenvironment. Humana, Clifton, pp. 33-104.
17. Johanson, C.E. (1989) Potential for pharmacologic manipulation of the blood-cerebrospinal fluid barrier. In: E.A. Neuwelt (Ed.), Implications of the blood-brain barrier and its manipulation. Plenum, New York, pp. 223-260.
18. Spector, R. (1986) Nucleoside and vitamin homeostasis in the mammalian central nervous system. Ann. N.Y. Acad. Sci. 481, 221-230.
19. Spector, R. (1989) Micronutrient homeostasis in mammalian brain and cerebrospinal fluid. J. Neurochem. 53, 1667-1674.
20. Collins, J.M. and Dedrick, R.L. (1983) Distributed model for drug delivery to CSF and brain tissue. Am. J. Physiol. 245, R303-R310.
21. Collins, J.M. (1983) Pharmacokinetics of intracerebroventricular administration. J. Neuro-Oncol. 1, 283-291.
22. Matsushita, H., Suzuki, H., Sugiyama, Y., Sawada, Y., Iga, T., Kawaguchi, T. and Hanano, M. (1991) Facilitated transport of cefodizime into the rat central nervous system. J. Pharmacol. Exp. Ther. 259, 620-625.
23. Matsushita, H., Suzuki, H., Sugiyama, Y., Sawada, Y., Iga, T., Kawaguchi, T. and Hanano, M. (1992) Effect of benzylpenicillin on the disposition of cefodizime in rats: No net effect on total clearance due to decreased hepatobiliary clearance and increased renal clearance. J. Pharmacol. Exp. Ther. 260, 499-504.
24. Meuremans, A., Vicart, P., Henzel, D., Mohler, J. and Vulpillat, M. (1986) Cefsulodin penetration into rat brain: Extracellular versus total concentration. Chemotherapy 32, 393-398.
25. Lehmenkühler, A., Kersting, U. and Nicholson, C. (1988) Diffusion of penicillin in agar and cerebral cortex of the rat. Brain Res. 444, 181-183.
26. Patlak, C.S. and Fenstermacher, J.D. (1975) Measurement of dog blood-brain barrier transfer constants by ventriculocisternal perfusion. Am. J. Physiol. 229, 877-884.
27. Blasberg, R.G., Patlak, C.S. and Fenstermacher, J.D. (1975) Intrathecal chemotherapy; Brain tissue profiles after ventriculo-cisternal perfusion. J. Pharmacol. Exp. Ther. 195, 73-83.
28. Fenstermacher, J.D., Patlak, C.S. and Blasberg, R.G. (1974) Transport of material between brain extracellular fluid, brain cells and blood. Fed. Proc. 33, 2070-2074.
29. Fenstermacher, J.D. and Davson, H. (1982) Distribution of two model amino acids from cerebrospinal fluid to brain and blood. Am. J. Physiol. 242, F171-F180.
30. Fenstermacher, J.D. and Kaye, T. (1988) Drug "diffusion" within the brain. Ann. N.Y. Acad. Sci. 531, 29-39.
31. Covell, D.G., Narang, P.K. and Poplack, D.G. (1985) Kinetic model for disposition of 6-mercaptopurine in monkey plasma and cerebrospinal fluid. Am. J. Physiol. 248, R147-R156.
32. Rapoport, S.I., Ohno, K. and Pettigrew, K.D. (1979) Drug entry into the brain. Brain Res. 172, 354-359.
33. Berlin, R.D. (1969) Active transport by isolated choroid plexus. Science 163, 1194-1195.
34. Smith, Q.R. and Rapoport, S.I. (1986) Cerebrovascular permeability coefficients to sodium, potassium, and chloride. J. Neurochem. 46, 1732-1742.
35. Yano, Y., Yamaoka, K. and Tanaka, H. (1989) A nonlinear least squares program, MULTI(FILT), based on fast inverse Laplace transform for microcomputer. Chem. Pharm. Bull. 37, 1035-1038.
36. Suzuki, H., Sawada, Y., Sugiyama, Y., Iga, T. and Hanano, M. (1989) Facilitated transport of benzylpenicillin through the blood-brain barrier in rats. J. Pharmacobio-Dyn. 12, 182-185.
37. Ohno, K., Pettigrew, K.D. and Rapoport, S.I. (1978) Lower limits of cerebrovascular permeability to nonelectrolytes in the conscious rat. Am. J. Physiol. 235, H299-H307.
38. Pellogrino, L.J. and Cushman, A.J. (1967) A stereotaxic atlas of the rat brain. Meredith, New York.
39. Suzuki, H., Sawada, Y., Sugiyama, Y., Iga, T. and Hanano, M. (1985) Saturable transport of cimetidine from cerebrospinal fluid to blood in rats. J. Pharmacobio-Dyn. 8, 73-76.
40. Cserr, H.F. and Berman, B.J. (1978) Iodide and thiocyanate efflux from brain following injection into the rat caudate nucleus. Am. J. Physiol. 235, F331-F337.
41. Nohjoh, T., Suzuki, H., Sawada, Y., Sugiyama, Y., Iga, T. and Hanano, M. (1989) Transport of cefodizime, a novel third generation cephalosporin antibiotic, in isolated rat choroid plexus. J. Pharmacol. Exp. Ther. 250, 324-328.
42. Cserr, H.F., Cooper, D.N., Suri, P.K. and Patlak, C.S. (1981) Efflux of radiolabeled polyethylene glycols and albumin from rat brain. Am. J. Physiol. 240, F319-F328.
43. Takasato, Y., Rapoport, S.I. and Smith, Q.R. (1984) An in situ brain perfusion technique to study cerebrovascular transport in the rat. Am. J. Physiol. 247. H484-H493.
44. Levin, V.A. (1980) Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability. J. Med. Chem. 23, 682-684.
45. Zlokovic, B.V. (1995) Cerebrovascular permeability to peptides: Manipulations of transport systems at blood-brain barrier. Pharm. Res. 12, 1395-1406.
46. Bickel, U. (1995) Antibody delivery through the blood-brain barrier. Adv. Drug Deliv. Rev. 15, 53-72.
47. Boado, R.J. (1995) Antisense drug delivery through the blood-brain barrier. Adv. Drug Deliv. Rev. 15, 73-107.
48. Morrison, S.L. and Shin, S.-U. (1995) Genetically engineered antibodies and their application to brain delivery. Adv. Drug Deliv. Rev. 15, 147-175.
49. Spector, R. (1987) Ceftriaxone transport through the blood-brain barrier. J. Infect. Dis. 156, 209-211.
50. Suzuki, H., Sawada, Y., Sugiyama, Y., Iga, T., Hanano, M. and Spector, R. (1989) Transport of imipenem, a novel carbapenem antibiotic, in the rat central nervous system. J. Pharmacol. Exp. Ther. 250, 979-984.
51. Lapointe, J.R., Beliveau, C., Chicoine, L. and Joncas, J.H. (1984) A comparison of ampicillin-cefotaxime and ampicillin-chloramphenicol in childhood bacterial meningitis: An experience in 55 patients. J. Antimicrob. Chemother. 14 (Suppl. B), 167-180.
52. McCracken, G.H., Nelson, J.D., Kaplan, S.L., Overturf, G.D., Rodrigues, W.H. and Steele, R.W. (1987) Antimicrobial therapy for bacterial meningitis in infants and children. Pediatr. Infect. Dis. J. 6, 501-505.
53. Kobayashi, Y., Haruta, T. and Okura, K. (1984) Cerebrospinal fluid penetration after combined administration of cefotaxime and ampicillin to rabbits with staphylococcal meningitis. J. Antimicrob. Chemother. 14 (Suppl. B), 125-134.
54. Okura, K., Haruta, T. and Kobayashi, Y. (1984) Pharmacokinetics in the cerebrospinal fluid after simultaneous administration of latamoxef and ampicillin to rabbit with staphylococcal meningitis. Jpn. J. Antibiot. 37, 1637-1646.
55. Okura, K., Haruta, T. and Kobayashi, Y. (1988) Drug transfer into cerebrospinal fluid after simultaneous administration of ampicillin with ceftriaxone or ceftazidime in rabbits with Staphylococcus aureus meningitis. J. Antimicrob. Chemother. 22, 207-211.
56. Okura, K., Haruta, T. and Kobayashi, Y. (1989) Experimental study on transfer ability to cerebrospinal fluid of cefodizime in combination with ampicillin. Jpn. J. Antibiot. 42, 1286-1292.
57. Haruta, T., Okura, K., Kuroki, S., Yamamoto, H. and Kobayashi, Y. (1989) Transfer ability of cefodizime to cerebrospinal fluid of rabbits with meningitis caused by Staphylococcus aureus. Jpn. J. Antibiot. 42, 1279-1285.
58. Spector, R. and Lorenzo, A.V. (1974) The effects of salicylate and probenecid on the cerebrospinal fluid transport of penicillin, aminosalicylic acid and iodide. J. Pharmacol. Exp. Ther. 188, 55-65.
59. Spector, R. and Lorenzo, A.V. (1974) Inhibition of penicillin transport from the cerebrospinal fluid after intracisternal inoculation of bacteria. J. Clin. Invest. 54, 316-325.
60. Cornford, E.M., Diep, C.P. and Pardridge, W.M. (1985) Blood-brain barrier transport of valproic acid. J. Neurochem. 44, 1541-1550.
61. Adkison, K.D.K., Artru, A.A., Powers, K.M. and Shen, D.D. (1994) Contribution of probenecid-sensitive anion transport processes at the brain capillary endothelium and choroid plexus to the efficient efflux of valproic acid from the central nervous system. J. Pharmacol. Exp. Ther. 268, 797-805.
62. Leininger, B., Ghersi-Egea, J.-F., Siest, G. and Minn, A. (1991) In vivo study of the elimination from rat brain of an intracerebrally formed xenobiotic metabolite, 1-naphthyl-p-glucuronide. J. Neurochem. 56, 1163-1168.
63. Dykstra, K.H., Arya, A., Arriola, D.M., Bungay, P.M., Morrison, P.F. and Dedrick, R.L. (1993) Microdialysis study of zidovudine (AZT) transport in rat brain. J. Pharmacol. Exp. Ther. 267, 1227-1236.
64. Deguchi, Y., Inabe, K., Tomiyasu, K., Nozawa, K., Yamada, S. and Kimura, R. (1995) Study on brain interstitial fluid distribution and blood-brain barrier transport of baclofen in rats by microdialysis. Pharm. Res. 12, 1838-1844.
65. Kakee, A., Terasaki, T. and Sugiyama, Y. (1996) Brain efflux index as a novel method of analyzing efflux transport at the blood-brain barrier. J. Phamacol. Exp. Ther. 277, 1550-1559.
66. Kakee, A., Terasaki, T. and Sugiyama, Y. (1995) Organic anion transport system acting as an efflux pump at the blood-brain barrier: Demonstration by a newly developed brain efflux index (BEI) method. Proc. Int. Symp. Control. Release Bioact. Mater., pp. 15-16.
67. Kitazawa, T., Terasaki, T., Kakee, A. and Sugiyama, Y. (1995) Carrier-mediated efflux transport of bile acid at the blood-brain barrier. Proc. AFMC Int. Med. Chem. Symp., pp. 210.
68. Kitazawa, T., Terasaki, T., Kakee, A. and Sugiyama, Y. (1995) Bile acid efflux transport mechanism from the brain across the blood-brain barrier. Proc. 3rd U.S.-Japan symposium on drug delivery systems, pp. 29.
69. Kitazawa, T., Terasaki, T., Kakee, A. and Sugiyama, Y. (1996) Bile acid efflux transport system at the blood-brain barrier: Demonstration by the brain efflux index (BEI) method. Proc. Int. Symp. Control. Release Bioact. Mater. 23, 433-434.
70. Banks, W.A., Kastin, A.J., Sam, H.M., Cao, V.T., King, B., Maness, L.M. and Schally, A.V. (1994) Saturable efflux of the peptides RC-160 and Tyr-MIF-1 by different parts of the blood-brain barrier. Brain Res. Bull. 35, 179-182.
71. Banks, W.A. and Kastin, A.J. (1990) Peptide transport systems for opiates across the blood-brain barrier. Am. J. Physiol. 259, E1-E10.
72. Cordon-Cardo, C., O'Brien, J.P., Casals, D., Rittman-Grauer, L., Biedler, J.L., Melamed, M.R. and Bertino, J.R. (1989) Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood-brain barrier sites. Proc. Natl. Acad. Sci. U.S.A. 86, 695-698.
73. Sugawara, I., Hamada, H., Tsuruo, T. and Mori, S. (1990) Specialized localization of P-glycoprotein recognized by MRK 16 monoclonal antibody in endothelial cells of the brain and the spinal cord. Jpn. J. Cancer Res. 81, 727-730.
74. Tsuji, A., Terasaki, T., Takabatake, Y., Tenda, Y., Tamai, I., Yamashita, T., Moritani, S., Tsuruo, T. and Yamashita, J. (1992) P-glycoprotein as the drug efflux pump in primary cultured bovine brain capillary endothelial cells. Life Sci. 51, 1427-1437.
75. Tatsuta, T., Naito, M., Oh-hara, T., Sugawara, I. and Tsuruo, T. (1992) Functional involvement of P-glycoprotein in blood-brain barrier. J. Biol. Chem. 267, 20383-20391.
76. 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. and Borst, P. (1994) Disruption of the mouse mdrla P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 77, 491-502.
77. Oude Elferink, R.P.J., Meijer, D.K.F., Kuipers, F., Jansen, P.L.M., Groen, A.K. and Groothuis, G.M.M. (1995) Hepatobiliary secretion of organic compounds; molecular mechanisms of membrane transport. Biochim. Biophys. Acta 1241, 215-268.
78. Yamazaki, M., Suzuki, H. and Sugiyama, Y. (1996) Recent advances in carrier-mediated hepatic uptake and biliary excretion of xenobiotics. Pharm. Res, 13, 497-513.
79. Mayer, R., Kartenbeck J., Büchler, M., Jedlitschky, G., Leier, I. and Keppler, D. (1995) Expression of the MRP gene-encoded conjugated export pump in liver and its selective absence from the canalicular membrane in transport deficient mutant hepatocytes. J. Cell Biol. 131, 137-150.
80. Ito, K., Suzuki, H., Hirohashi, T., Kume, K., Shimizu, T. and Sugiyama, Y. (1996) Expression of a putative ATP-binding cassette region, homologous to that in multidrug resistance associated protein (MRP), is hereditarily defective in Eisai hyperbilirubinemic rats (EHBR). Int. Hepatol. Commun. 4, 291-298.
81. Paulusma, C.C., Bosma, P.J., Zaman, G.J.R., Bakker, C.T.M., Otter, M., Scheffer, G.L., Scheper, R.J., Borst, P. and Oude Elferink, R.P.J. (1996) Congenital jaundice in rats with a mutation in a multidrug resistance-associated protein gene. Science 271, 1126-1128.
82. Jedlitschky, G., Leier, I., Buchholz, U., Center, M. and Keppler, D. (1994) ATP-dependent transport of glutathione S-conjugates by the multidrug resistance-associated protein. Cancer Res. 54, 4833-4836.
83. 4 and structually related conjugates. J. Biol. Chem. 269, 27807-27810.
84. Müller, M., Meijer, C., Zaman, G.J.R., Borst, P., Scheper, R.J., Mulder, N.H., de Vries, E.G.E, and Jansen, P.L.M. (1994) Overexpression of the gene encoding the multidrug resistance-associated protein results in increased ATP-dependent glutathione S-conjugates transport. Proc. Natl. Acad. Sci. U.S.A. 91, 13033-13037.
85. Pappenheimer, J.R., Heisey, S.R. and Jordan, E.F. (1961) Active transport of Diodrast and phenolsulfophthalein from cerebrospinal fluid to blood. Am. J. Physiol. 200, 1-10.
86. Davson, H., Kleeman, C.R. and Levine, E. (1962) Quantitative studies of the passage of different substances out of the cerebrospinal fluid. J. Physiol. 161, 126-142.
87. 131I and PAH across the cerebrospinal fluid-blood barrier. J. Physiol. 167, 239-246.
88. Pollay, M. and Davson, H. (1963) The passage of certain substances out of the cerebrospinal fluid. Brain 86, 137-150.
89. Ashcroft, G.W., Dow, R.C. and Moir, A.T.B. (1968) The active transport of 5-hydroxyindol-3-ylacetic acid and 3-methoxy-4-hydroxyphenylacetic acid from a recirculatory perfusion system of the cerebral ventricles of the unanesthetized dog. J.Physiol. 199, 397-425.
90. Cserr, H. and Van Dyke, D.H. (1971) 5-Hydroxyindoleacetic acid accumulation by isolated choroid plexus. Am. J. Physiol. 220, 718-723.
91. Forn, J. (1972) Active transport of 5-hydroxyindoleacetic acid by the rabbit choroid plexus in vitro. Biochem. Pharmacol. 21, 619-624.
92. Rollins, D.E. and Reed, D.J. (1970) Transport of DMO out of cerebrospinal fluid of rats. Am. J. Physiol. 219, 1200-1204.
93. Spector, R. and Lorenzo, A.V. (1973) The active transport of para-aminosalicylic acid from the cerebrospinal fluid. J. Pharmacol. Exp. Ther. 185, 642-648.
94. Rubin, R., Owens, F. and Rail, D. (1968) Transport of methotrexate by the choroid plexus. Cancer Res. 28, 689-694.
95. Fishman, R.A. (1966) Blood-brain and CSF barriers to penicillin and related organic acids. Arch. Neurol. 15, 113-124.
96. 14C-penicillin from cerebrospinal fluid to blood. J. Pharm. Sci. 58, 1106-1109.
97. Spector, R. (1986) Ceftriaxone pharmacokinetics in the central nervous system. J. Pharmacol. Exp. Ther. 236, 380-383.
98. Pritchard, J.B. (1980) Accumulation of anionic pesticides by rabbit choroid plexus in vitro. J. Pharmacol. Exp. Ther. 212, 354-359.
99. Kim, C.S. and Pritchard, J.B. (1993) Transport of 2,4,5-trichlorophenoxy-acetic acid across the blood-cerebrospinal fluid barrier of the rabbit. J. Pharmacol. Exp. Ther. 267, 751-757.
100. Kahan, F.M., Kropp, H., Sundelof, J.G. and Birnbaum, J. (1983) Thienamycin: Development of imipenem-cilastatin. J. Antimicrob. Chemother. 12 (Suppl. D), 1-35.
101. Birnbaum, J., Kahan, F.M., Kroppp, H. and MacDonald, J.S. (1985) Carbapenems, a new class of beta-lactam antibiotics. Discovery and development of imipenem/cilastatin. Am. J. Med. 78 (Suppl. 6A), 3-21.
102. Suzuki, H., Sawada, Y., Sugiyama, Y., Iga, T. and Hanano, M. (1987) Transport of benzylpenicillin by the rat choroid plexus in vitro. J. Pharmacol. Exp. Ther. 242, 660-665.
103. Suzuki, H., Sawada, Y., Sugiyama, Y., Iga, T. and Hanano, M. (1987) Anion exchanger mediates benzylpenicillin transport in rat choroid plexus. J. Pharmacol. Exp, Ther. 243, 1147-1152.
104. Suzuki, H., Sawada, Y., Sugiyama, Y., Iga, T. and Hanano, M. (1986) Transport of cimetidine by the rat choroid plexus in vitro. J. Pharmacol. Exp. Ther. 239, 927-935.
105. Ogawa, M., Suzuki, H., Sawada, Y., Hanano, M. and Sugiyama, Y. (1994) Kinetics of active efflux via choroid plexus of β-lactam antibiotics from the CSF into the circulation. Am. J. Physiol. 266, R392-R399.
106. Smith, Q.R., Momma, S., Aoyagi, M. and Rapoport, S.I. (1987) Kinetics of neutral amino acid transport across the blood-brain barrier. J. Neurochem. 49, 1651-1658.
107. Ullrich, K.J. (1994) Specificity of transporters for "organic anions" and "organic cations" in the kidney. Biochim. Biophys. Acta 1197, 45-62.
108. Spector, R. (1980) Riboflavin transport in the central nervous system: Characterization and effects of drugs. J. Clin. Invest. 66, 821-831.
109. Bresler, S.E., Bresler, V.M., Kazbekov, E.N., Nikiforov, A.A. and Vasilieva, N.N. (1979) On the active transport of organic acids (fluorescein) in the choroid plexus of the rabbit. Biochim. Biophys. Acta 550, 110-119.
110. Carter-Su, C. and Kimmich, G.A. (1979) Membrane potentials and sugar transport by ATP-depleted intestinal cells: Effect of anion gradients. Am. J. Physiol. 237, C67-C74.
111. Roch-Ramel, F., Besseghir, K. and Murer, H. (1992) In: E.E. Windhager (Ed.), Handbook of Physiology, Section 8, Renal Physiology, Vol. II. Oxford University Press, New York, pp. 2189-2262.
112. Pritchard, J.B. and Miller, D.S. (1993) Mechanisms mediating renal secretion of organic anions and cations. Physiol. Rev. 73, 765-796.
113. Dantzler, W.H. and Wright, S.H. (1997) Renal tubular secretion of organic anions. Adv. Drug. Deliv. Rev. 25, 217-230.
114. Johanson, C.E. (1984) Differential effects of acetazolamide, benzolamide and systemic acidosis on hydrogen and bicarbonate gradients across the apical and basolateral membranes of the choroid plexus. J. Pharmacol. Exp. Ther. 231, 502-511.
115. Smith, Q.R. and Johanson, C.E. (1985) Active transport of chloride by lateral ventricle choroid plexus of the rat. Am. J. Physiol. 249, F470-F477.
116. 3 exchange in choroid plexus: Analysis by the DMO method for cell pH. Am. J. Physiol. 249, F478-F484.
117. Aronson, P.S. (1981) Identifying secondary active solute transport in epithelia. Am. J. Physiol. 240, F1-F11.
118. Christ, W. (1990) Central nervous system toxicity of quinolones: human and animal findings. J. Antimicrob. Chemother. 26 (Suppl. B), 219-225.
119. Shiba, K., Saito, A., Shimada, J., Hori, S., Kaji, M., Miyahara, T., Kusajima, H., Kaneko, S., Saito, S., Ooie, T. and Uchida, H. (1990) Renal handling of fleroxacin in rabbits, dogs, and humans. Antimicrob. Agents Chemother. 34, 58-64.
120. Ooie, T., Suzuki, H., Terasaki, T. and Sugiyama, Y. (1996) Characterization of the transport properties of a quinolone antibiotic, fleroxacin, in rat choroid plexus. Pharm. Res. 13, 523-527.
121. Okano, T., Maegawa, H., Inui, K. and Hori, R. (1990) Interaction of ofloxacin with organic cation transport system in rat renal brush-border membranes. J. Pharmacol. Exp. Ther. 255, 1033-1037.
122. Ooie, T., Suzuki, H., Terasaki, T. and Sugiyama, Y. (1996) Kinetics of quinolone antibiotics in rats: Efflux from cerebrospinal fluid to the circulation. Pharm. Res. 13, 1065-1068.
123. Ooie, T., Suzuki, H., Terasaki, T. and Sugiyama, Y. (1996) Comparative distribution of quinolone antibiotics in cerebrospinal fluid (CSF) and brain in rats and dogs. J. Pharmacol. Exp. Ther. 278, 590-596.
124. Pritchard, J.B. and Miller, D.S. (1997) Renal secretion of organic cations: a multi process. Adv. Drug Deliv. Rev. 25, 231-242.
125. Gründemann, D., Gorboulev, V., Gambaryan, S., Veyhl, M. and Koepsell, H. (1994) Drug excretion mediated by a new prototype of polyspecific transporter. Nature 372, 549-552.
126. Schanker, L.S., Prockop, L.D., Schou, J. and Sisodia, P. (1962) Rapid efflux of some quaternary ammonium compounds from cerebrospinal fluid. Life Sci. 10, 515-521.
127. Lanman, R.C. and Schanker, L.S. (1980) Transport of choline out of the cranial cerebrospinal fluid spaces of the rabbit. J. Pharmacol. Exp. Ther. 215, 563-568.
128. Tochino, Y. and Schanker, L.S. (1965) Active transport of quaternary ammonium compounds by the choroid plexus in vitro. Am. J. Physiol. 208, 666-673.
129. Miller, T.B. and Ross, C.R. (1976) Transport of organic cations and anions by choroid plexus. J. Pharmacol. Exp. Ther. 196, 771-777.
130. Suzuki, H., Sawada, Y., Sugiyama, Y., Iga, T. and Hanano, M. (1986) Comparative uptake of cimetidine by rat choroid plexus between the lateral and the 4th ventricles. J. Pharmacobio-Dyn. 9, 327-329.
131. Suzuki, H., Sawada, Y., Sugiyama, Y., Iga, T. and Hanano, M. (1988) Efflux of cimetidine from the rat cerebrospinal fluid. Drug Metab. Dispos. 16, 328-330.
132. 2-antagonists: Past, present and future. J. Clin. Gastroenterol. 5 (Suppl. 1), 71-79.
133. 2-receptor antagonists and gastric acid secretion. Pharmacol. Ther. 26, 221-234.
134. Cantu, T.G. and Korek, J.S. (1991) Central nervous system reactions to histamine-2 receptor blockers. Ann. Int. Med. 114, 1027-1034.
135. Schentag, J.J., Cerra, F.B., Calleri, G.M., Leising, M.E., French, M.A. and Bernhard, H. (1981) Age, disease, and cimetidine disposition in healthy subjects and chronically ill patients. Clin. Pharmacol. Ther. 29, 737-743.
136. Ziemniak, J.A., Shank, R.G. and Schentag, J.J. (1984) The partitioning of cimetidine into canine cerebrospinal fluid. Drug Metab. Dispos. 12, 217-221.
137. Cserr, H.F. (1965) Potassium exchange between cerebrospinal fluid, plasma, and brain. Am. J. Physiol. 209, 1219-1226.
138. Whittico, M.T. and Giacomini, K.M. (1988) Cimetidine elimination from the cerebrospinal fluid of the rat. Pharm. Res. 5, 628-633.
139. Spector, R. and Snodgrass, S.R. (1976) The effect of uremia on penicillin flux between blood and cerebrospinal fluid. J. Lab. Clin. Med. 87, 749-759.
140. Moroni, F., Lombardi, G., Carla, V., Pellegrini, D., Carassale, G.L. and Cortesini, C. (1986) Content of quinolinic acid and of other tryptophan metabolites increases in brain regions of rats used as experimental models of hepatic encephalopathy. J. Neurochem. 46, 869-874.
141. Moroni, F., Lombardi, G., Carla, V., Lal, S., Etienne, P. and Nair, N.P.V. (1986) Increase in the content of quinolinic acid in cerebrospinal fluid and frontal cortex of patients with hepatic failure. J. Neurochem. 47, 1667-1671.
142. McKinney, T.D., Myers, P. and Speeg, K.V. Jr. (1981) Cimetidine secretion by rabbit renal tubules in vitro. Am. J. Physiol. 241, F69-F76.
143. McKinney, T.D. and Kunnemann, M.E. (1987) Cimetidine transport in rabbit renal cortical brush-border membrane vesicles. Am. J. Physiol. 252, F525-F535.
144. Gisclon, L.G., Wong, F.M. and Giacomini, K.M. (1987) Cimetidine transport in isolated luminal membrane vesicles from rabbit kidney. Am. J. Physiol. 253, F141-F150.
145. Gisclon, L.G., Boyd, R.A., Williams, R.L. and Giacomini, K.M. (1989) The effect of probenecid on the renal elimination of cimetidine. Clin. Pharmacol. Ther. 45, 444-452.
146. Hsyu, P.-H., Gisclon, L.G., Hui, A.C. and Giacomini, K.M. (1988) Interactions of organic anions with the organic cation transporter in renal BBMV. Am. J. Physiol. 254, F56-F61.
147. Ott, R.J., Hai, A.C. and Giacomini, K.M. (1990) Mechanisms of interactions between organic anions and the organic cation transporter in renal brush border membrane vesicles. Biochem. Pharmacol. 40, 659-661.
148. Ullrich, K.J., Rumrich, G., David, C. and Fritzsch, G. (1993) Bisubstrates: substances that interact with renal contraluminal organic anion and organic cation transport systems. I. Amines, piperidines, piperazines, azepines, pyridines, quinolines, imidazoles, thiazoles, guanidines and hydrazines. Pflug. Arch. Eur. J. Physiol. 425, 280-299.
149. Ullrich, K.J., Rumrich, G., David, C. and Fritzsch, G. (1993) Bisubstrates: substances that interact with renal contraluminal organic anion and organic cation transport systems. II. Zwitterionic substrates: dipeptides, cephalosporins, quinolone-carboxylate gyrase inhibitors and phosphamide thiazine carboxylates; nonionizable substrates: steroid hormones and cyclophosphamides. Pflug. Arch. Eur. J. Physiol. 425, 300-312.
150. Ullrich, K.J., Fritzsch, G., Rumrich, G. and David, C. (1994) Polysubstrates: Substances that interact with renal contraluminal PAH, sulfate and MNeN transport: Sulfamoyl-, sulfonylurea-, thiazide- and benzeneamino-carboxylate (Nicotinate) compounds. J. Pharmacol. Exp. Ther. 269, 684-692.
151. Bossuyt, X., Muller, M., Hagenbuch, B. and Meier, P.J. (1996) Polyspecific drug and steroid clearance by an organic anion transporter of mammalian liver. J. Pharmacol. Exp. Ther. 276, 891-896.
152. Whittico, M.T., Yuan, G. and Giacomini, K.M. (1990) Cimetidine transport in isolated brush border membrane vesicles from bovine choroid plexus. J. Pharmacol. Exp. Ther. 255, 615-623.
153. Twentyman, P.R. and Bleehen, N.M. (1991) Resistance modification by PSC-833, a novel non-immunosuppressive cyclosporin A. Eur. J. Cancer 27, 1639-1642.
154. Boote, D.J., Dennis, I.F., Twentyman, P.R., Osborne, R.J., Laburte, C., Hensel, S., Smyth, J.F., Brampton, M.H. and Bleehen, N.M. (1996) Phase I study of etoposide with SDZ PSC 833 as a modulator of multidrug resistance in patients with cancer. J. Clin. Oncol. 14, 610-618.
155. Audus, K.L. and Borchatdt, R.T. (1987) Bovine brain microvessel endothelial cell monolayers as a model system for the blood-brain barrier. Ann. N.Y. Acad. Sci. 507, 9-18.
156. Mayer, S.E. and Sanders-Bush, E. (1993) Sodium-dependent antiporters in choroid plexus epithelial cultures from rabbit. J. Neurochem. 60, 1308-1316.
157. Ramanathan, V.K., Hui, A.C., Brett, C.M. and Giacomini, K.M. (1996) Primary cell culture of the rabbit choroid plexus: An experimental system to investigate membrane transport. Pharm. Res. 13, 952-956.
158. Lindsey, A.E., Schneider, K., Simmons, D.M., Baron, R., Lee, B.S. and Kopito, R.R. (1990) Functional expression and subcellular localization of an anion exchanger cloned from choroid plexus. Proc. Natl. Acad. Sci. U.S.A. 87, 5278-5282.
159. Schreiber, G. and Aldred, A.R. (1993) Molecular cloning of choroid plexus-specific transport proteins. In: W.M. Pardridge (Ed.), The blood-brain barrier. Raven, New York, pp. 441-459.