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Combining PET biodistribution and equilibrium dialysis assays to assess the free brain concentration and BBB transport of CNS drugs

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Combining PET biodistribution and equilibrium dialysis assays to assess the free brain concentration and BBB transport of CNS drugs. / Gunn, Roger N.; Summerfield, Scott G.; Salinas, Cristian A.; Read, Kevin D.; Guo, Qi; Searle, Graham E.; Parker, Christine A.; Jeffrey, Phil; Laruelle, Marc.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 32, No. 5, 05.2012, p. 874-883.

Research output: Contribution to journalArticle

Harvard

Gunn, RN, Summerfield, SG, Salinas, CA, Read, KD, Guo, Q, Searle, GE, Parker, CA, Jeffrey, P & Laruelle, M 2012, 'Combining PET biodistribution and equilibrium dialysis assays to assess the free brain concentration and BBB transport of CNS drugs' Journal of Cerebral Blood Flow and Metabolism, vol 32, no. 5, pp. 874-883., 10.1038/jcbfm.2012.1

APA

Gunn, R. N., Summerfield, S. G., Salinas, C. A., Read, K. D., Guo, Q., Searle, G. E., ... Laruelle, M. (2012). Combining PET biodistribution and equilibrium dialysis assays to assess the free brain concentration and BBB transport of CNS drugs. Journal of Cerebral Blood Flow and Metabolism, 32(5), 874-883. 10.1038/jcbfm.2012.1

Vancouver

Gunn RN, Summerfield SG, Salinas CA, Read KD, Guo Q, Searle GE et al. Combining PET biodistribution and equilibrium dialysis assays to assess the free brain concentration and BBB transport of CNS drugs. Journal of Cerebral Blood Flow and Metabolism. 2012 May;32(5):874-883. Available from: 10.1038/jcbfm.2012.1

Author

Gunn, Roger N.; Summerfield, Scott G.; Salinas, Cristian A.; Read, Kevin D.; Guo, Qi; Searle, Graham E.; Parker, Christine A.; Jeffrey, Phil; Laruelle, Marc / Combining PET biodistribution and equilibrium dialysis assays to assess the free brain concentration and BBB transport of CNS drugs.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 32, No. 5, 05.2012, p. 874-883.

Research output: Contribution to journalArticle

Bibtex - Download

@article{5fcd134b2f96434a840e765fb866dc2f,
title = "Combining PET biodistribution and equilibrium dialysis assays to assess the free brain concentration and BBB transport of CNS drugs",
author = "Gunn, {Roger N.} and Summerfield, {Scott G.} and Salinas, {Cristian A.} and Read, {Kevin D.} and Qi Guo and Searle, {Graham E.} and Parker, {Christine A.} and Phil Jeffrey and Marc Laruelle",
year = "2012",
doi = "10.1038/jcbfm.2012.1",
volume = "32",
number = "5",
pages = "874--883",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",

}

RIS (suitable for import to EndNote) - Download

TY - JOUR

T1 - Combining PET biodistribution and equilibrium dialysis assays to assess the free brain concentration and BBB transport of CNS drugs

A1 - Gunn,Roger N.

A1 - Summerfield,Scott G.

A1 - Salinas,Cristian A.

A1 - Read,Kevin D.

A1 - Guo,Qi

A1 - Searle,Graham E.

A1 - Parker,Christine A.

A1 - Jeffrey,Phil

A1 - Laruelle,Marc

AU - Gunn,Roger N.

AU - Summerfield,Scott G.

AU - Salinas,Cristian A.

AU - Read,Kevin D.

AU - Guo,Qi

AU - Searle,Graham E.

AU - Parker,Christine A.

AU - Jeffrey,Phil

AU - Laruelle,Marc

PY - 2012/5

Y1 - 2012/5

N2 - <p>The passage of drugs in and out of the brain is controlled by the blood brain barrier (BBB), typically, using either passive diffusion across a concentration gradient or active transport via a protein carrier. In-vitro and preclinical measurements of BBB penetration do not always accurately predict the in-vivo situation in humans. Thus, the ability to assay the concentration of novel drug candidates in the human brain in vivo provides valuable information for derisking of candidate molecules early in drug development. Here, positron emission tomography (PET) measurements are combined with in-vitro equilibrium dialysis assays to enable assessment of transport and estimation of the free brain concentration in vivo. The PET and equilibrium dialysis data were obtained for 36 compounds in the pig. Predicted P-glycoprotein (P-gp) status of the compounds was consistent with the PET/equilibrium dialysis results. In particular, Loperamide, a well-known P-gp substrate, exhibited a significant concentration gradient consistent with active efflux and after inhibition of the P-gp process the gradient was removed. The ability to measure the free brain concentration and assess transport of novel compounds in the human brain with combined PET and equilibrium dialysis assays can be a useful tool in central nervous system (CNS) drug development. Journal of Cerebral Blood Flow &amp; Metabolism (2012) 32, 874-883; doi:10.1038/jcbfm.2012.1; published online 25 January 2012</p>

AB - <p>The passage of drugs in and out of the brain is controlled by the blood brain barrier (BBB), typically, using either passive diffusion across a concentration gradient or active transport via a protein carrier. In-vitro and preclinical measurements of BBB penetration do not always accurately predict the in-vivo situation in humans. Thus, the ability to assay the concentration of novel drug candidates in the human brain in vivo provides valuable information for derisking of candidate molecules early in drug development. Here, positron emission tomography (PET) measurements are combined with in-vitro equilibrium dialysis assays to enable assessment of transport and estimation of the free brain concentration in vivo. The PET and equilibrium dialysis data were obtained for 36 compounds in the pig. Predicted P-glycoprotein (P-gp) status of the compounds was consistent with the PET/equilibrium dialysis results. In particular, Loperamide, a well-known P-gp substrate, exhibited a significant concentration gradient consistent with active efflux and after inhibition of the P-gp process the gradient was removed. The ability to measure the free brain concentration and assess transport of novel compounds in the human brain with combined PET and equilibrium dialysis assays can be a useful tool in central nervous system (CNS) drug development. Journal of Cerebral Blood Flow &amp; Metabolism (2012) 32, 874-883; doi:10.1038/jcbfm.2012.1; published online 25 January 2012</p>

U2 - 10.1038/jcbfm.2012.1

DO - 10.1038/jcbfm.2012.1

M1 - Article

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 5

VL - 32

SP - 874

EP - 883

ER -

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