Large variation in brain exposure of reference CNS drugs: A PET study in nonhuman primates

International Journal of Neuropsychopharmacology

Volumn 18, Issue 10, 2015, Pages

  Schou, Magnus ^a   Varnäs, Katarina ^a   Lundquist, Stefan ^a,b   Nakao, Ryuji ^a   Amini, Nahid ^a   Takano, Akihiro ^a   Finnema, Sjoerd J ^a   Halldin, Christer ^a   Farde, Lars ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

^b ASTRAZENECA R AND D   (Sweden)

Author keywords

CNS; Microdosing; PET

Indexed keywords

CAFFEINE; CAFFEINE C 11; CARBON 11; CENTRAL NERVOUS SYSTEM AGENTS; CITALOPRAM; CITALOPRAM C 11; CLOMIPRAMINE; CLOMIPRAMINE C 11; CLOZAPINE; CLOZAPINE C 11; DIAZEPAM; DIAZEPAM C 11; DOXEPIN; DOXEPIN C 11; MORPHINE; MORPHINE C 11; NICOTINE; NICOTINE C 11; RADIOISOTOPE; SELEGILINE; SELEGILINE C 11; SERTRALINE; SERTRALINE C 11; SULPIRIDE; SULPIRIDE C 11; UNCLASSIFIED DRUG; VENLAFAXINE; VENLAFAXINE C 11; VERAPAMIL; VERAPAMIL C 11; CARBON; RADIOPHARMACEUTICAL AGENT;

ANIMAL EXPERIMENT; ANIMAL TISSUE; AREA UNDER THE CURVE; ARTICLE; BRAIN; CONTROLLED STUDY; DRUG DIFFUSION; DRUG DISTRIBUTION; DRUG HALF LIFE; DRUG METABOLISM; FEMALE; MAXIMUM PLASMA CONCENTRATION; MICRODOSIMETRY; NONHUMAN; PARTITION COEFFICIENT; PLASMA; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; RADIOACTIVITY; TIME TO MAXIMUM PLASMA CONCENTRATION; ANIMAL; BIOLOGICAL MODEL; CHEMICAL MODEL; DIAGNOSTIC IMAGING; DOSE RESPONSE; DRUG EFFECTS; MACACA FASCICULARIS; METABOLISM; RHESUS MONKEY;

ANIMALS; BRAIN; CARBON RADIOISOTOPES; CENTRAL NERVOUS SYSTEM AGENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; MACACA FASCICULARIS; MACACA MULATTA; MODELS, BIOLOGICAL; MODELS, CHEMICAL; MORPHINE; POSITRON-EMISSION TOMOGRAPHY; RADIOPHARMACEUTICALS; SULPIRIDE; VERAPAMIL;

EID: 84983787551     PISSN: 14611457     EISSN: 14695111     Source Type: Journal    
DOI: 10.1093/ijnp/pyv036     Document Type: Article

References (34)

1. Akaike H (1992) [Data analysis by statistical models]. No To Hat-tatsu 24:127-133.
2. Arrowsmith J (2011) Trial watch: Pphase II failures: 2008-2010. Nat Rev Drug Discov 10:328-329.
3. Bergstrom M, Grahnen A, Langstrom B (2003) Positron emission tomography microdosing: a new concept with application in tracer and early clinical drug development. Eur J Clin Pharmacol 59:357-366.
4. Di L, Umland JP, Chang G, Huang Y, Lin Z, Scott DO, Troutman MD, Liston TE (2011) Species independence in brain tissue binding using brain homogenates. Drug Metab Dispos 39:1270-1277.
5. Farde L, Eriksson L, Blomquist G, Halldin C (1989) Kinetic analysis of central [11C]raclopride binding to D2-dopamine receptors studied by PET-a comparison to the equilibrium analysis. J Cereb Blood Flow Metab 9:696-708.
6. Farde L, Ito H, Swahn CG, Pike VW, Halldin C (1998) Quantitative analyses of carbonyl-carbon-11-WAY-100635 binding to central 5-hydroxytryptamine-1A receptors in man. J Nucl Med 39:1965-1971.
7. Fowler JS, MacGregor RR, Wolf AP, Arnett CD, Dewey SL, Schlyer D, Christman D, Logan J, Smith M, Sachs H, et al. (1987) Mapping human brain monoamine oxidase A and B with 11C-labeled suicide inactivators and PET. Science 235:481-485.
8. Friden M, Bergstrom F, Wan H, Rehngren M, Ahlin G, Ham-marlund-Udenaes M, Bredberg U (2011) Measurement of unbound drug exposure in brain: modeling of pH partitioning explains diverging results between the brain slice and brain homogenate methods. Drug Metab Dispos 39:353-362.
9. Friden M, Wennerberg M, Antonsson M, Sandberg-Ställ M, Farde L, Schou M (2014) Identifcation of positron emission tomography (PET) tracer candidates by prediction of the target-bound fraction in the brain. EJNMMI Res 4:50.
10. Gex-Fabry M, Haffen E, Paintaud G, Bizouard P, Sechter D, Bech-tel PR, Balant LP (2000) Population pharmacokinetics of clo-mipramine, desmethylclomipramine, and hydroxylated metabolites in patients with depression receiving chronic treatment: model evaluation. Ther Drug Monit 22:701-711.
11. Gunn RN, Summerfeld SG, Salinas CA, Read KD, Guo Q, Searle GE, Parker CA, Jeffrey P, Laruelle M (2012) Combining PET bio-distribution and equilibrium dialysis assays to assess the free brain concentration and BBB transport of CNS drugs. J Cereb Blood Flow Metab 32:874-883.
12. Halldin C, Gulyas B, Farde L (2001) PET studies with carbon-11 radioligands in neuropsychopharmacological drug development. Current Pharmaceutical Design 7:1907-1929.
13. Huang SC, Feng DG, Phelps ME (1986) Model dependency and estimation reliability in measurement of cerebral oxygen utilization rate with oxygen-15 and dynamic positron emission tomography. J Cereb Blood Flow Metab 6:105-119.
14. Hukkanen J, Jacob P, 3rd, Benowitz NL (2005) Metabolism and disposition kinetics of nicotine. Pharmacol Rev 57:79-115.
15. Innis RB, Carson R (2007) Consensus nomenclature: its time has come. Eur J Nucl Med Mol Imaging 34:1239.
16. Kalvass JC, Maurer TS, Pollack GM (2007) Use of plasma and brain unbound fractions to assess the extent of brain distribution of 34 drugs: comparison of unbound concentration ratios to in vivo p-glycoprotein effux ratios. Drug Metab Dispos 35:660-666.
17. Karlsson P, Farde L, Halldin C, Swahn CG, Sedvall G, Foged C, Hansen KT, Skrumsager B (1993) PET examination of [11C]NNC 687 and [11C]NNC 756 as new radioligands for the D1-dopa-mine receptor. Psychopharmacology (Berl) 113:149-156.
18. Kola I, Landis J (2004) Can the pharmaceutical industry reduce attrition rates? Nat Rev Drug Discov 3:711-715.
19. Lammertsma AA, Bench CJ, Price GW, Cremer JE, Luthra SK, Tur-ton D, Wood ND, Frackowiak RS (1991) Measurement of cerebral monoamine oxidase B activity using L-[11C]deprenyl and dynamic positron emission tomography. J Cereb Blood Flow Metab 11:545-556.
20. Lappin G (2010) Microdosing: current and the future. Bioanalysis 2:509-517.
21. Lee CM, Farde L (2006) Using positron emission tomography to facilitate CNS drug development. Trends Pharmacol Sci 27:310-316.
22. Leenders KL, Perani D, Lammertsma AA, Heather JD, Buckingham P, Healy MJ, Gibbs JM, Wise RJ, Hatazawa J, Herold S, et al. (1990) Cerebral blood fow, blood volume and oxygen utilization. Normal values and effect of age. Brain 113:27-47.
23. Maurer TS, Debartolo DB, Tess DA, Scott DO (2005) Relationship between exposure and nonspecifc binding of thirty-three central nervous system drugs in mice. Drug Metab Dispos 33:175-181.
24. Mintun MA, Raichle ME, Kilbourn MR, Wooten GF, Welch MJ (1984) A quantitative model for the in vivo assessment of drug binding sites with positron emission tomography. Ann Neurol 15:217-227.
25. Mochizuki H, Kimura Y, Ishii K, Oda K, Sasaki T, Tashiro M, Yanai K, Ishiwata K (2004) Simplifed PET measurement for evaluating histamine H1 receptors in human brains using [11C]dox-epin. Nucl Med Biol 31:1005-1011.
26. Osman S, Lundkvist C, Pike VW, Halldin C, McCarron JA, Swahn CG, Farde L, Ginovart N, Luthra SK, Gunn RN, Bench CJ, Sargent PA, Grasby PM (1998) Characterisation of the appearance of radioactive metabolites in monkey and human plasma from the 5-HT1A receptor radioligand, [carbonyl-11C]WAY-100635-explanation of high signal contrast in PET and an aid to biomathematical modelling. Nucl Med Biol 25:215-223.
27. Qian XD, Beck WT (1990) Binding of an optically pure photoaffn-ity analogue of verapamil, LU-49888, to P-glycoprotein from multidrug-resistant human leukemic cell lines. Cancer Res 50:1132-1137.
28. Rollema H, Shrikhande A, Ward KM, Tingley FD, 3rd, Coe JW, O'Neill BT, Tseng E, Wang EQ, Mather RJ, Hurst RS, Williams KE, de Vries M, Cremers T, Bertrand S, Bertrand D (2010) Preclinical properties of the alpha4beta2 nicotinic acetylcholine receptor partial agonists varenicline, cytisine and dianicline translate to clinical effcacy for nicotine dependence. Br J Pharmacol 160:334-345.
29. Shimomura K, Kamata O, Ueki S, Ida S, Oguri K (1971) Analgesic effect of morphine glucuronides. Tohoku J Exp Med 105:45-52.
30. Suhara T, Sudo Y, Yoshida K, Okubo Y, Fukuda H, Obata T, Yoshi-kawa K, Suzuki K, Sasaki Y (1998) Lung as reservoir for anti-depressants in pharmacokinetic drug interactions. Lancet 351:332-335.
31. Summerfeld SG, Read K, Begley DJ, Obradovic T, Hidalgo IJ, Cog-gon S, Lewis AV, Porter RA, Jeffrey P (2007) Central nervous system drug disposition: the relationship between in situ brain permeability and brain free fraction. J Pharmacol Exp Ther 322:205-213.
32. Varrone A, Sjoholm N, Eriksson L, Gulyas B, Halldin C, Farde L (2009) Advancement in PET quantifcation using 3D-OP-OSEM point spread function reconstruction with the HRRT. Eur J Nucl Med Mol Imaging 36:1639-1650.
33. Wong DF, Wagner HN Jr, Tune LE, Dannals RF, Pearlson GD, Links JM, Tamminga CA, Broussolle EP, Ravert HT, Wilson AA, Toung JK, Malat J, Williams JA, O'Tuama LA, Snyder SH, Kuhar MJ, Gjedde A (1986) Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science 234:1558-1563.
34. Xie R, Hammarlund-Udenaes M, de Boer AG, de Lange EC (1999) The role of P-glycoprotein in blood-brain barrier transport of morphine: transcortical microdialysis studies in mdr1a (-/-) and mdr1a (+/+) mice. Br J Pharmacol 128:563-568.