The use of healthy volunteers instead of patients to inform drug dosing studies: A [11C]raclopride PET study

Psychopharmacology

Volumn 217, Issue 4, 2011, Pages 515-523

  Kim, Euitae ^a,b,c   Howes, Oliver D ^b,c   Kim, Bo Hyung ^a   Yu, Kyung Sang ^a   Jeong, Jae Min ^a   Lee, Jae Sung ^a   Kim, Su Jin ^a   Jang, In Jin ^a   Park, Jung Shin ^d   Kim, Yong Gil ^d   Shin, Sang Goo ^a   Turkheime, Federico E ^e   Kapur, Shitij ^c   Kwon, Jun Soo ^a,f  

^a Seoul National University College of Medicine   (South Korea)

^b HAMMERSMITH HOSPITAL   (United Kingdom)

^c KING'S COLLEGE LONDON   (United Kingdom)

^d SK Holdings Co Ltd   (South Korea)

^e IMPERIAL COLLEGE LONDON   (United Kingdom)

^f Seoul National University   (South Korea)

Author keywords

Antipsychotics; Biomarker; Dopamine D2 receptor; Drug development; Positron emission tomography; Subject selection

Indexed keywords

BROMPERIDOL; CHLORPROMAZINE; CLOZAPINE; DOPAMINE 1 RECEPTOR; DOPAMINE 2 RECEPTOR; DOPAMINE RECEPTOR; HALOPERIDOL; NEUROLEPTIC AGENT; OLANZAPINE; PIMOZIDE; RACLOPRIDE C 11; RISPERIDONE; SEROTONIN 2A RECEPTOR; UNCLASSIFIED DRUG; YKP 1358; ZOTEPINE;

ADULT; AREA UNDER THE CURVE; ARTICLE; BINDING AFFINITY; BLOOD SAMPLING; CEREBELLUM; CLINICAL ARTICLE; CONTROLLED STUDY; DOSE CALCULATION; DRUG BLOOD LEVEL; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG HALF LIFE; FEMALE; HUMAN; IMAGE ANALYSIS; LIGAND BINDING; MALE; MAXIMUM PLASMA CONCENTRATION; NUCLEAR MAGNETIC RESONANCE IMAGING; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; PUTAMEN; RECEPTOR OCCUPANCY; SCHIZOPHRENIA; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION;

EID: 85027949947     PISSN: 00333158     EISSN: 14322072     Source Type: Journal    
DOI: 10.1007/s00213-011-2306-4     Document Type: Article

References (29)

1. Arakawa R, Ito H, Takano A, Takahashi H, Morimoto T, Sassa T, Ohta K, Kato M, Okubo Y, Suhara T (2008) Dose-finding study of paliperidone ER based on striatal and extrastriatal dopamine D2 receptor occupancy in patients with schizophrenia. Psychopharmacology (Berl) 197:229-235
2. Arakawa R, Ito H, Takano A, Okumura M, Takahashi H, Takano H, Okubo Y, Suhara T (2010) Dopamine D2 receptor occupancy by perospirone: a positron emission tomography study in patients with schizophrenia and healthy subjects. Psychopharmacology (Berl) 209:285-290
3. Bench CJ, Lammertsma AA, Dolan RJ, Grasby PM, Warrington SJ, Gunn K, Cuddigan M, Turton DJ, Osman S, Frackowiak RS (1993) Dose dependent occupancy of central dopamine D2 receptors by the novel neuroleptic CP-88,059-01: a study using positron emission tomography and 11C-raclopride. Psychopharmacology (Berl) 112:308-314 (Pubitemid 23278294)
4. Burt DR, Creese I, Snyder SH (1977) Antischizophrenic drugs: chronic treatment elevates dopamine receptor binding in brain. Science 196:326-328 (Pubitemid 8076966)
5. Catafau AM, Penengo MM, Nucci G, Bullich S, Corripio I, Parellada E, Garcia-Ribera C, Gomeni R, Merlo-Pich E (2008) Pharmacokinetics and time-course of D(2) receptor occupancy induced by atypical antipsychotics in stabilized schizophrenic patients. J Psychopharmacol 22:882-894
6. Ginovart N, Wilson AA, Hussey D, Houle S, Kapur S (2009) D2- receptor upregulation is dependent upon temporal course of D2- occupancy: a longitudinal [11C]-raclopride PET study in cats. Neuropsychopharmacology 34:662-671
7. Howes OD, Egerton A, Allan V, McGuire P, Stokes P, Kapur S (2009) Mechanisms underlying psychosis and antipsychotic treatment response in schizophrenia: insights from PET and SPECT imaging. Curr Pharm Des 15:2550-2559
8. Inoue M, Suhara T, Sudo Y, Okubo Y, Yasuno F, Kishimoto T, Yoshikawa K, Tanada S (2001) Age-related reduction of extrastriatal dopamine D2 receptor measured by PET. Life Sci 69:1079-1084 (Pubitemid 32701918)
9. Ito H, Hietala J, Blomqvist G, Halldin C, Farde L (1998) Comparison of the transient equilibrium and continuous infusion method for quantitative PET analysis of [11C]raclopride binding. J Cereb Blood Flow Metab 18:941-950
10. Kapur S, Zipursky R, Jones C, Remington G, Houle S (2000) Relationship between dopamine D(2) occupancy, clinical response, and side effects: a double-blind PET study of firstepisode schizophrenia. Am J Psychiatry 157:514-520 (Pubitemid 30191189)
11. Kegeles LS, Slifstein M, Frankle WG, Xu X, Hackett E, Bae SA, Gonzales R,KimJH, Alvarez B,Gil R, LaruelleM, Abi-DarghamA (2008) Dose-occupancy study of striatal and extrastriatal dopamine D2 receptors by aripiprazole in schizophrenia with PET and [18F]fallypride. Neuropsychopharmacology 33:3111-3125
12. Kim E, Howes OD, Yu KS et al (2011) Calculating occupancy when one does not have the baseline-a comparison of different options. J Cereb Blood Flow Metab (in press)
13. Lammertsma AA, Hume SP (1996) Simplified reference tissue model for PET receptor studies. Neuroimage 4:153-158
14. Laruelle M (1998) Imaging dopamine transmission in schizophrenia. A review and meta-analysis. Q J Nucl Med 42:211-221 (Pubitemid 28529874)
15. Lee T, Seeman P, Tourtellotte WW, Farley IJ, Hornykeiwicz O (1978) Binding of 3H-neuroleptics and 3H-apomorphine in schizophrenic brains. Nature 274:897-900 (Pubitemid 9004058)
16. Lim KS, Kwon JS, Jang IJ, Jeong JM, Lee JS, Kim HW, KangWJ, Kim JR, Cho JY, Kim E, Yoo SY, Shin SG, Yu KS (2007) Modeling of brain D2 receptor occupancy-plasma concentration relationships with a novel antipsychotic, YKP1358, using serial PET scans in healthy volunteers. Clin Pharmacol Ther 81:252-258 (Pubitemid 46174822)
17. Mackay AV, Iversen LL, Rossor M, Spokes E, Bird E, Arregui A, Creese I, Synder SH (1982) Increased brain dopamine and dopamine receptors in schizophrenia. Arch Gen Psychiatry 39:991-997 (Pubitemid 12020980)
18. Mamo D, Graff A, Mizrahi R, Shammi CM, Romeyer F, Kapur S (2007) Differential effects of aripiprazole on D(2), 5-HT(2), and 5-HT(1A) receptor occupancy in patients with schizophrenia: a triple tracer PET study. Am J Psychiatry 164:1411-1417 (Pubitemid 47461142)
19. Mamo DC, Uchida H, Vitcu I, Barsoum P, Gendron A, Goldstein J, Kapur S (2008) Quetiapine extended-release versus immediaterelease formulation: a positron emission tomography study. J Clin Psychiatry 69:81-86 (Pubitemid 351282000)
20. McGuire P, Howes OD, Stone J, Fusar-Poli P (2008) Functional neuroimaging in schizophrenia: diagnosis and drug discovery. Trends Pharmacol Sci 29:91-98
21. Olsson H, Farde L (2001) Potentials and pitfalls using high affinity radioligands in PET and SPET determinations on regional drug induced D2 receptor occupancy-a simulation study based on experimental data. Neuroimage 14:936-945 (Pubitemid 32929894)
22. Pien HH, Fischman AJ, Thrall JH, Sorensen AG (2005) Using imaging biomarkers to accelerate drug development and clinical trials. Drug Discov Today 10:259-266 (Pubitemid 40222219)
23. Pleuvry BJ (2008) Hysteresis in drug response. Anaesth Intensive Care Medicine 9:372-373
24. Silvestri S, Seeman MV, Negrete J-C, Houle S, Shammi CM, Remington GJ, Kapur S, Zipursky RB, Wilson AA, Christensen BK, Seeman P (2000) Increased dopamine D 2 receptor binding after long-term treatment with antipsychotics in humans: a clinical PET study. Psychopharmacology 152:174-180
25. Sparshatt A, Taylor D, Patel MX, Kapur S (2010) A systematic review of aripiprazole-dose, plasma concentration, receptor occupancy, and response: implications for therapeutic drug monitoring. J Clin Psychiatry 71:1447-1456
26. Tauscher J, Jones C, Remington G, Zipursky RB, Kapur S (2002) Significant dissociation of brain and plasma kinetics with antipsychotics. Mol Psychiatry 7:317-321 (Pubitemid 34280640)
27. Uchida H, Kapur S, Mulsant BH, Graff-Guerrero A, Pollock BG, Mamo DC (2009) Sensitivity of older patients to antipsychotic motor side effects: a PET study examining potential mechanisms. Am J Geriatr Psychiatry 17:255-263
28. Vernaleken I, Fellows C, Janouschek H, Brocheler A, Veselinovic T, Landvogt C, Boy C, BuchholzHG, SpreckelmeyerK, Bartenstein P, Cumming P, Hiemke C, Rosch F, Schafer W, Wong DF, Grunder G (2008) Striatal and extrastriatal D2/D3-receptorbinding properties of ziprasidone: a positron emission tomography study with [18F]fallypride and [11C]raclopride (D2/D3- receptor occupancy of ziprasidone). J Clin Psychopharmacol 28:608-617
29. Wong DF, Pearlson GD, Tune LE, Young LT, Meltzer CC, DannalsRF, Ravert HT, Reith J, Kuhar MJ, Gjedde A (1997) Quantification of neuroreceptors in the living human brain: IV. Effect of aging and elevations of D2-like receptors in schizophrenia and bipolar illness. J Cereb Blood Flow Metab 17:331-342 (Pubitemid 27161376)