Predicting brain occupancy from plasma levels using PET: Superiority of combining pharmacokinetics with pharmacodynamics while modeling the relationship

Journal of Cerebral Blood Flow and Metabolism

Volumn 32, Issue 4, 2012, Pages 759-768

  Kim, Euitae ^a,b,c   Howes, Oliver D ^b,c   Kim, Bo Hyung ^a   Jeong, Jae Min ^a   Lee, Jae Sung ^a   Jang, In Jin ^a   Shin, Sang Goo ^a   Turkheimer, Federico E ^b   Kapur, Shitij ^c   Kwon, Jun Soo ^a,d  

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

^b IMPERIAL COLLEGE LONDON   (United Kingdom)

^c KING'S COLLEGE LONDON   (United Kingdom)

^d Seoul National University   (South Korea)

Author keywords

Antipsychotics; dopamine receptor occupancy; pharmacodynamics; pharmacokinetics; positron emission tomography

Indexed keywords

ARIPIPRAZOLE; DOPAMINE RECEPTOR; RACLOPRIDE C 11;

ADULT; ARTICLE; BLOOD LEVEL; BRAIN; BRAIN COMPUTER INTERFACE; CONFIDENCE INTERVAL; HUMAN; HYSTERESIS; MALE; NORMAL HUMAN; PLASMA; PLASMA CONCENTRATION-TIME CURVE; POSITRON EMISSION TOMOGRAPHY; PRIORITY JOURNAL; SINGLE BLIND PROCEDURE; SINGLE DRUG DOSE;

ADULT; ANTIPSYCHOTIC AGENTS; BRAIN; HUMANS; MALE; MODELS, THEORETICAL; PIPERAZINES; POSITRON-EMISSION TOMOGRAPHY; QUINOLONES; RECEPTORS, DOPAMINE; TIME FACTORS;

EID: 84859426128     PISSN: 0271678X     EISSN: 15597016     Source Type: Journal    
DOI: 10.1038/jcbfm.2011.180     Document Type: Article

References (38)

1. Abanades S, van der Aart J, Barletta JA, Marzano C, Searle GE, Salinas CA, Ahmad JJ, Reiley RR, Pampols-Maso S, Zamuner S, Cunningham VJ, Rabiner EA, Laruelle MA, Gunn RN (2011) Prediction of repeat-dose occupancy from single-dose data: characterisation of the relationship between plasma pharmacokinetics and brain target occupancy. J Cereb Blood Flow Metab 31:944-52
2. Alvan G, Paintaud G, Wakelkamp M (1999) The efficiency concept in pharmacodynamics. Clin Pharmacokinet 36:375-89 (Pubitemid 29261512)
3. Bressan RA, Erlandsson K, Spencer EP, Ell PJ, Pilowsky LS (2004) Prolactinemia is uncoupled from central D2/D3 dopamine receptor occupancy in amisulpride treated patients. Psychopharmacology (Berl) 175:367-73 (Pubitemid 39361925)
4. Chen Y, Dalwadi G, Benson HA (2004) Drug delivery across the blood-brain barrier. Curr Drug Deliv 1:361-76
5. de Greef R, Maloney A, Olsson-Gisleskog P, Schoemaker J, Panagides J (2011) Dopamine d(2) occupancy as a biomarker for antipsychotics: quantifying the relationship with efficacy and extrapyramidal symptoms. AAPS J 13:121-30
6. First MB, Spitzer RL, Miriam G, Williams BWJ (2002) Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Non-patient Edition (SCID-I/NP). New York: Biometrics Research, New York State Psychiatry Institute
7. Fischman AJ, Alpert NM, Rubin RH (2002) Pharmacokinetic imaging: a noninvasive method for determining drug distribution and action. Clin Pharmacokinet 41: 581-602 (Pubitemid 34848364)
8. Grunder G, Fellows C, Janouschek H, Veselinovic T, Boy C, Brocheler A, Kirschbaum KM, Hellmann S, Spreckelmeyer KM, Hiemke C, Rosch F, Schaefer WM, Vernaleken I (2008) Brain and plasma pharmacokinetics of aripiprazole in patients with schizophrenia: an [18F]fallypride PET study. Am J Psychiatry 165:988-95
9. Holford NH, Sheiner LB (1981a) Understanding the doseeffect relationship: clinical application of pharmacokinetic-pharmacodynamic models. Clin Pharmacokinet 6:429-53 (Pubitemid 12213270)
10. Holford NH, Sheiner LB (1981b) Pharmacokinetic and pharmacodynamic modeling in vivo. Crit Rev Bioeng 5:273-322
11. 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 15:2550-9
12. 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 18:941-50
13. Kapur S, Langlois X, Vinken P, Megens AA, De Coster R, Andrews JS (2002) The differential effects of atypical antipsychotics on prolactin elevation are explained by their differential blood-brain disposition: a pharmacological analysis in rats. J Pharmacol Exp Ther 302: 1129-34 (Pubitemid 34920235)
14. Kapur S, Seeman P (2000) Antipsychotic agents differ in how fast they come off the dopamine D2 receptors. Implications for atypical antipsychotic action. J Psychiatry Neurosci 25:161-6 (Pubitemid 30233553)
15. 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 first-episode schizophrenia. Am J Psychiatry 157:514-20 (Pubitemid 30191189)
16. Kegeles LS, Slifstein M, Frankle WG, Xu X, Hackett E, Bae SA, Gonzales R, Kim JH, Alvarez B, Gil R, Laruelle M, Abi-Dargham A (2008) Dose-occupancy study of striatal and extrastriatal dopamine D2 receptors by aripiprazole in schizophrenia with PET and [18F]fallypride. Neuropsychopharmacology 33:3111-25
17. Kim JR, Seo HB, Cho JY, Kang DH, Kim YK, Bahk WM, Yu KS, Shin SG, Kwon JS, Jang IJ (2008) Population pharmacokinetic modelling of aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patients. Br J Clin Pharmacol 66:802-10
18. Kirschbaum KM, Uhr M, Holthoewer D, Namendorf C, Pietrzik C, Hiemke C, Schmitt U (2010) Pharmacokinetics of acute and sub-chronic aripiprazole in P-glycoprotein deficient mice. Neuropharmacology 59: 474-9
19. Lammertsma AA, Hume SP (1996) Simplified reference tissue model for PET receptor studies. Neuroimage 4:153-8
20. Lim KS, Kwon JS, Jang IJ, Jeong JM, Lee JS, Kim HW, Kang WJ, Kim JR, Cho JY, Kim E, Yoo SY, Shin SG, Yu KS (2007) Modeling of brain D2 receptor occupancyplasma concentration relationships with a novel antipsychotic, YKP1358, using serial PET scans in healthy volunteers. Clin Pharmacol Ther 81:252-8 (Pubitemid 46174822)
21. Locatelli I, Kastelic M, Koprivsek J, Kores-Plesnicar B, Mrhar A, Dolzan V, Grabnar I (2010) A population pharmacokinetic evaluation of the influence of CYP2D6 genotype on risperidone metabolism in patients with acute episode of schizophrenia. Eur J Pharm Sci 41: 289-98
22. Mamo D, Kapur S, Shammi CM, Papatheodorou G, Mann S, Therrien F, Remington G (2004) A PET study of dopamine D2 and serotonin 5-HT2 receptor occupancy in patients with schizophrenia treated with therapeutic doses of ziprasidone. Am J Psychiatry 161:818-25 (Pubitemid 38625334)
23. McGuire P, Howes OD, Stone J, Fusar-Poli P (2008) Functional neuroimaging in schizophrenia: diagnosis and drug discovery. Trends Pharmacol Sci 29:91-8
24. Meibohm B, Derendorf H (1997) Basic concepts of pharmacokinetic/ pharmacodynamic (PK/PD) modelling. Int J Clin Pharmacol Ther 35:401-13 (Pubitemid 27462583)
25. Mensch J, Jaroskova L, Sanderson W, Melis A, Mackie C, Verreck G, Brewster ME, Augustijns P (2010) Application of PAMPA-models to predict BBB permeability including efflux ratio, plasma protein binding and physicochemical parameters. Int J Pharm 395:182-97
26. 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 14:936-45 (Pubitemid 32929894)
27. Peng T, Zysk J, Dorff P, Elmore CS, Strom P, Malmquist J, Ding M, Tuke D, Werkheiser J, Widzowski D, Mrzljak L, Maier D (2010) D2 receptor occupancy in conscious rat brain is not significantly distinguished with [3H]-MNPA, [3H]-(+)-PHNO, and [3H]-raclopride. Synapse 64:624-33
28. Pien HH, Fischman AJ, Thrall JH, Sorensen AG (2005) Using imaging biomarkers to accelerate drug development and clinical trials. Drug Discov Today 10:259-66 (Pubitemid 40222219)
29. Pleuvry BJ (2008) Hysteresis in drug response. Anaesth Intensive Care Med 9:372-3
30. Remington G, Mamo D, Labelle A, Reiss J, Shammi C, Mannaert E, Mann S, Kapur S (2006) A PET study evaluating dopamine D2 receptor occupancy for longacting injectable risperidone. Am J Psychiatry 163: 396-401 (Pubitemid 44469380)
31. Samtani MN, Vermeulen A, Stuyckens K (2009) Population pharmacokinetics of intramuscular paliperidone palmitate in patients with schizophrenia: a novel oncemonthly, long-acting formulation of an atypical antipsychotic. Clin Pharmacokinet 48:585-600
32. Schmidt KC, Turkheimer FE (2002) Kinetic modeling in positron emission tomography. Q J Nucl Med 46: 70-85 (Pubitemid 34808740)
33. Schoemaker RC, van Gerven JM, Cohen AF (1998) Estimating potency for the Emax-model without attaining maximal effects. J Pharmacokinet Biopharm 26:581-93 (Pubitemid 29157784)
34. Seeman P, Lee T (1975) Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 188:1217-9
35. Sheiner LB, Stanski DR, Vozeh S, Miller RD, Ham J (1979) Simultaneous modeling of pharmacokinetics and pharmacodynamics: application to d-tubocurarine. Clin Pharmacol Ther 25:358-71 (Pubitemid 9164953)
36. Tauscher J, Jones C, Remington G, Zipursky RB, Kapur S (2002) Significant dissociation of brain and plasma kinetics with antipsychotics. Mol Psychiatry 7:317-21 (Pubitemid 34280640)
37. Vernaleken I, Fellows C, Janouschek H, Brocheler A, Veselinovic T, Landvogt C, Boy C, Buchholz HG, Spreckelmeyer K, Bartenstein P, Cumming P, Hiemke C, Rosch F, Schafer W, Wong DF, Grunder G (2008) Striatal and extrastriatal D2/D3-receptor-binding properties of ziprasidone: a positron emission tomography study with [18F]Fallypride and [11C]raclopride (D2/D3-receptor occupancy of ziprasidone). J Clin Psychopharmacol 28:608-17
38. Willmann JK, van Bruggen N, Dinkelborg LM, Gambhir SS (2008) Molecular imaging in drug development. Nat Rev Drug Discov 7:591-607 (Pubitemid 351927724)