Associating in vitro target binding and in vivo CNS occupancy of serotonin reuptake inhibitors in rats: The role of free drug concentrations

Xenobiotica

Volumn 42, Issue 3, 2012, Pages 256-265

  Bundgaard, Christoffer ^a   Sveigaard, Christina ^a   Brennum, Lise T ^a   Stensbøl, Tine B ^a  

^a H LUNDBECK A S   (Denmark)

Author keywords

Bloodbrain barrier; Free fraction; P glycoprotein; Pharmacokinetics; SERT occupancy; SSRI

Indexed keywords

CITALOPRAM; DULOXETINE; PAROXETINE; SEROTONIN TRANSPORTER; SERTRALINE; VENLAFAXINE;

ANIMAL EXPERIMENT; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG BRAIN LEVEL; DRUG RECEPTOR BINDING; DRUG STRUCTURE; IN VITRO STUDY; IN VIVO STUDY; LIPOPHILICITY; MALE; NONHUMAN; RAT;

ANIMALS; BRAIN; CELL LINE; CENTRAL NERVOUS SYSTEM; DOGS; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; HYDROGEN-ION CONCENTRATION; INHIBITORY CONCENTRATION 50; MALE; RATS; RATS, SPRAGUE-DAWLEY; REFERENCE STANDARDS; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; SEROTONIN UPTAKE INHIBITORS; SUBCELLULAR FRACTIONS;

RATTUS;

EID: 84856398719     PISSN: 00498254     EISSN: 13665928     Source Type: Journal    
DOI: 10.3109/00498254.2011.618953     Document Type: Article

References (36)

1. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. (2010). Structure and function of the blood-brain barrier. Neurobiol Dis 37:13-25.
2. Andersen PH, Nielsen EB, Grønvald FC, Braestrup C. (1986). Some atypical neuroleptics inhibit [3H]SCH 23390 binding in vivo. Eur J Pharmacol 120:143-144. (Pubitemid 16134695)
3. Becker S, Liu X. (2006). Evaluation of the utility of brain slice methods to study brain penetration. Drug Metab Dispos 34:855-861.
4. Bøgesø KB, Bregnedal P, Juhl K, Wiborg O, Zong H, Topiol S. (2010). New naphthalene derivatives of citalopram discriminate between the primary and the allosteric binding sites at the human serotonin transporter. Presented at 16th World Congress on Basic and Clinical Pharmacology, Copenhagen, July 17-23.
5. Bøgesø KB, Hyttel J, Christensen AV, Arnt J, Liljefors T. (1986). Chirality as determinant for neuroleptic or antidepressant action of drugs. In: Harms AF, ed. Innovative approaches in drug researC.H. Amsterdam: Elsevier, 371-392.
6. Dallas S, Miller DS, Bendayan R. (2006). Multidrug resistanceassociated proteins: Expression and function in the central nervous system. Pharmacol Rev 58:140-161.
7. Danhof M, de Jongh J, De Lange EC, Della Pasqua O, Ploeger BA, Voskuyl RA. (2007). Mechanism-based pharmacokineticpharmacodynamic modeling: Biophase distribution, receptor theory, and dynamical systems analysis. Annu Rev Pharmacol Toxicol 47:357-400.
8. de Lange EC, Ravenstijn PG, Groenendaal D, van Steeg TJ. (2005). Toward the prediction of CNS drug-effect profiles in physiological and pathological conditions using microdialysis and mechanism-based pharmacokinetic- pharmacodynamic modeling. AAPS J 7:532-543.
9. 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.
10. Fridén M, Bergström F, Wan H, Rehngren M, Ahlin G, Hammarlund-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.
11. Fridén M, Gupta A, Antonsson M, Bredberg U, Hammarlund-Udenaes M. (2007). In vitro methods for estimating unbound drug concentrations in the brain interstitial and intracellular fluids. Drug Metab Dispos 35:1711-1719. (Pubitemid 47296068)
12. Hammarlund-Udenaes M. (2010). Active-site concentrations of chemicals-are they a better predictor of effect than plasma/organ/tissue concentrations?. Basic Clin Pharmacol Toxicol 106:215-220.
13. Hammarlund-Udenaes M, Fridén M, Syvänen S, Gupta A. (2008). On the rate and extent of drug delivery to the brain. Pharm Res 25:1737-1750.
14. Jeffrey P, Summerfield SG. (2007). Challenges for blood-brain barrier (BBB) screening. Xenobiotica 37:1135-1151. (Pubitemid 350041554)
15. Kalvass JC, Maurer TS. (2002). Influence of nonspecific brain and plasma binding on CNS exposure: Implications for rational drug discovery. Biopharm Drug Dispos 23:327-338. (Pubitemid 36124162)
16. Kalvass JC, Olson ER, Cassidy MP, Selley DE, Pollack GM. (2007). Pharmacokinetics and pharmacodynamics of seven opioids in P-glycoprotein- competent mice: Assessment of unbound brain EC50,u and correlation of in vitro, preclinical, and clinical data. J Pharmacol Exp Ther 323:346-355. (Pubitemid 47443282)
17. Kaufmann AM, Krise JP. (2007). Lysosomal sequestration of aminecontaining drugs: Analysis and therapeutic implications. J Pharm Sci 96:729-746. (Pubitemid 46657864)
18. Large CH, Kalinichev M, Lucas A, Carignani C, Bradford A, Garbati N, Sartori I, Austin NE, Ruffo A, Jones DN, Alvaro G, Read KD. (2009). The relationship between sodium channel inhibition and anticonvulsant activity in a model of generalised seizure in the rat. Epilepsy Res 85:96-106.
19. Larsen AK, Brennum LT, Egebjerg J, Sánchez C, Halldin C, Andersen PH. (2004). Selectivity of (3)H-MADAM binding to 5-hydroxytryptamine transporters in vitro and in vivo in mice; correlation with behavioural effects. Br J Pharmacol 141:1015-1023. (Pubitemid 38510085)
20. Lin JH. (2006). Tissue distribution and pharmacodynamics: A complicated relationship. Curr Drug Metab 7:39-65.
21. Linnet K, Ejsing TB. (2008). A review on the impact of P-glycoprotein on the penetration of drugs into the brain. Focus on psychotropic drugs. Eur Neuropsychopharmacol 18:157-169.
22. Liu X, Chen C, Smith BJ. (2008). Progress in brain penetration evaluation in drug discovery and development. J Pharmacol Exp Ther 325:349-356. (Pubitemid 351574780)
23. Liu X, Van Natta K, Yeo H, Vilenski O, Weller PE, Worboys PD, Monshouwer M. (2009a). Unbound drug concentration in brain homogenate and cerebral spinal fluid at steady state as a surrogate for unbound concentration in brain interstitial fluid. Drug Metab Dispos 37:787-793.
24. Liu X, Vilenski O, Kwan J, Apparsundaram S, Weikert R. (2009b). Unbound brain concentration determines receptor occupancy: A correlation of drug concentration and brain serotonin and dopamine reuptake transporter occupancy for eighteen compounds in rats. Drug Metab Dispos 37:1548-1556.
25. Maurer TS, Debartolo DB, Tess DA, Scott DO. (2005). Relationship between exposure and non-specific binding of thirty-three central nervous system drugs in mice. Drug Metab Dispos 33:175-181. (Pubitemid 40023529)
26. Milletti F, Storchi L, Sforna G, Cruciani G. (2007). New and original pKa prediction method using grid molecular interaction fields. J Chem Inf Model 47:2172-2181. (Pubitemid 350275083)
27. Read KD, Braggio S. (2010). Assessing brain free fraction in early drug discovery. Expert Opin Drug Metab Toxicol 6:337-344.
28. Sánchez C, Kreilgaard M. (2004). R-citalopram inhibits functional and 5-HTP-evoked behavioural responses to the SSRI, escitalopram. Pharmacol Biochem Behav 77:391-398. (Pubitemid 38125173)
29. Smith DA, Di L, Kerns EH. (2010). The effect of plasma protein binding on in vivo efficacy: Misconceptions in drug discovery. Nat Rev Drug Discov 9:929-939.
30. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC. (1985). Measurement of protein using bicinchoninic acid. Anal Biochem 150:76-85. (Pubitemid 16258399)
31. Summerfield SG, Lucas AJ, Porter RA, Jeffrey P, Gunn RN, Read KR, Stevens AJ, Metcalf AC, Osuna MC, Kilford PJ, Passchier J, Ruffo AD. (2008). Toward an improved prediction of human in vivo brain penetration. Xenobiotica 38:1518-1535.
32. Summerfield SG, Read K, Begley DJ, Obradovic T, Hidalgo IJ, Coggon 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. (Pubitemid 46956363)
33. Summerfield SG, Stevens AJ, Cutler L, del Carmen Osuna M, Hammond B, Tang SP, Hersey A, Spalding DJ, Jeffrey P. (2006). Improving the in vitro prediction of in vivo central nervous system penetration: Integrating permeability, P-glycoprotein efflux, and free fractions in blood and brain. J Pharmacol Exp Ther 316:1282-1290. (Pubitemid 43345304)
34. Wan H, Rehngren M, Giordanetto F, Bergström F, Tunek A. (2007). High-throughput screening of drug-brain tissue binding and in silico prediction for assessment of central nervous system drug delivery. J Med Chem 50:4606-4615. (Pubitemid 47463235)
35. Watson J, Wright S, Lucas A, Clarke KL, Viggers J, Cheetham S, Jeffrey P, Porter R, Read KD. (2009). Receptor occupancy and brain free fraction. Drug Metab Dispos 37:753-760.
36. Westerhout J, Danhof M, De Lange EC. (2011). Preclinical prediction of human brain target site concentrations: Considerations in extrapolating to the clinical setting. J Pharm Sci 100:3577-3593.