Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Recent Update on Pharmacokinetics and Drug Metabolism in CNS-based Drug Discovery

Author(s): Sachin Nashik Sanap, Amol Chhatrapati Bisen, Ashwini Kedar, Sristi Agrawal and Rabi Sankar Bhatta*

Volume 29, Issue 20, 2023

Published on: 17 July, 2023

Page: [1602 - 1616] Pages: 15

DOI: 10.2174/1381612829666230707121415

Price: $65

Abstract

Despite significant advancements in CNS research, CNS illnesses are the most important and serious cause of mental disability worldwide. These facts show a tremendous unmet demand for effective CNS medications and pharmacotherapy since it accounts for more hospitalizations and extended care than practically all other disorders combined. The site-targeted kinetics of the brain and, pharmacodynamics of CNS effects are determined/regulated by various mechanisms after the dose, including blood-brain barrier (BBB) transport and many other processes. These processes are condition-dependent in terms of their rate and extent because they are dynamically controlled. For effective therapy, drugs should access the CNS “at the right place, time, and concentration”. Details on inter-species and inter-condition variances are required to translate target site pharmacokinetics and associated CNS effects between species and illness states, improving CNS therapeutics and drug development. The present review encircles a short discussion about the barriers that affect effective CNS treatment and precisely focuses on the pharmacokinetics aspects of efficient CNS therapeutics.

« Previous Next »
[1]
Leslie AK, Prabhu S. Drug delivery across the blood-brain barrier. Mol Pharm 2013; 10(5): 1471-2.
[2]
Masserini M. Nanoparticles for brain drug delivery. ISRN Biochem 2013; 2013: 1-18.
[http://dx.doi.org/10.1155/2013/238428] [PMID: 25937958]
[3]
Pulgar VM. Transcytosis to cross the blood brain barrier, new advancements and challenges. Front Neurosci 2019; 12: 1019.
[http://dx.doi.org/10.3389/fnins.2018.01019] [PMID: 30686985]
[4]
Kadry H, Noorani B, Cucullo L. A blood-brain barrier overview on structure, function, impairment, and biomarkers of integrity. Fluids Barriers CNS 2020; 17(1): 69.
[http://dx.doi.org/10.1186/s12987-020-00230-3] [PMID: 33208141]
[5]
Dong X. Current strategies for brain drug delivery. Theranostics 2018; 8(6): 1481-93.
[http://dx.doi.org/10.7150/thno.21254] [PMID: 29556336]
[6]
Warren KE. Beyond the blood: brain barrier: The importance of central nervous system (CNS) pharmacokinetics for the treatment of CNS tumors, including diffuse intrinsic pontine glioma. Front Oncol 2018; 8: 239.
[http://dx.doi.org/10.3389/fonc.2018.00239] [PMID: 30018882]
[7]
Bahadur S, Pathak K. Physicochemical and physiological considerations for efficient nose-to-brain targeting. Expert Opin Drug Deliv 2012; 9(1): 19-31.
[http://dx.doi.org/10.1517/17425247.2012.636801] [PMID: 22171740]
[8]
Ghadiri M, Young P, Traini D. Strategies to enhance drug absorption via nasal and pulmonary routes. Pharmaceutics 2019; 11(3): 113.
[http://dx.doi.org/10.3390/pharmaceutics11030113] [PMID: 30861990]
[9]
Upadhyay RK. Drug delivery systems, CNS protection, and the blood brain barrier. BioMed Res Int 2014; 2014: 1-37.
[http://dx.doi.org/10.1155/2014/869269] [PMID: 25136634]
[10]
Zhao Y, Gan L, Ren L, Lin Y, Ma C, Lin X. Factors influencing the blood-brain barrier permeability. Brain Res 2022; 1788: 869269.
[http://dx.doi.org/10.1016/j.brainres.2022.147937]
[11]
Hammarlund-Udenaes M, Fridén M, Syvänen S, Gupta A. On the rate and extent of drug delivery to the brain. Pharm Res 2008; 25(8): 1737-50.
[http://dx.doi.org/10.1007/s11095-007-9502-2] [PMID: 18058202]
[12]
Lindqvist A, Rip J, Gaillard PJ, Björkman S, Hammarlund-Udenaes M. Enhanced brain delivery of the opioid peptide DAMGO in glutathione pegylated liposomes: a microdialysis study. Mol Pharm 2013; 10(5): 1533-41.
[http://dx.doi.org/10.1021/mp300272a] [PMID: 22934681]
[13]
Lu CT, Zhao YZ, Wong HL, Cai J, Peng L, Tian XQ. Current approaches to enhance CNS delivery of drugs across the brain barriers. Int J Nanomedicine 2014; 9: 2241-57.
[http://dx.doi.org/10.2147/IJN.S61288] [PMID: 24872687]
[14]
Sweeney MD, Zhao Z, Montagne A, et al. Blood-brain barrier: from physiology to disease and back. Physiol Rev 2019; 99(1): 21-78.
[http://dx.doi.org/10.1152/physrev.00050.2017] [PMID: 30280653]
[15]
Haddad-Tóvolli R, Dragano NRV, Ramalho AFS, Velloso LA. Development and function of the blood-brain barrier in the context of metabolic control. Front Neurosci 2017; 11: 224.
[http://dx.doi.org/10.3389/fnins.2017.00224] [PMID: 28484368]
[16]
Daneman R, Prat A. The blood-brain barrier. Cold Spring Harb Perspect Biol 2015; 7(1): a020412.
[http://dx.doi.org/10.1101/cshperspect.a020412] [PMID: 25561720]
[17]
Rhea EM, Banks WA, Reagan L, Rhea EM. Role of the blood-brain barrier in central nervous system insulin resistance. Front Neurosci 2019; 13: 521.
[http://dx.doi.org/10.3389/fnins.2019.00521] [PMID: 31213970]
[18]
Solár P, Zamani A. Kubíčková L, Dubový P, Joukal M. Choroid plexus and the blood-cerebrospinal fluid barrier in disease. Fluids Barriers CNS 2020; 17(1): 35.
[http://dx.doi.org/10.1186/s12987-020-00196-2] [PMID: 32375819]
[19]
Battal B, Kocaoglu M, Bulakbasi N, Husmen G, Tuba Sanal H, Tayfun C. Cerebrospinal fluid flow imaging by using phase-contrast MR technique. Br J Radiol 2011; 84(1004): 758-65.
[http://dx.doi.org/10.1259/bjr/66206791] [PMID: 21586507]
[20]
Whedon JM. Cerebrospinal fluid stasis and its clinical significance. Altern Ther Health Med 2010; 15: 54-60.
[21]
Brinker T, Stopa E, Morrison J, Klinge P. A new look at cerebrospinal fluid circulation. Fluids Barriers CNS 2014; 11(1): 10.
[http://dx.doi.org/10.1186/2045-8118-11-10] [PMID: 24817998]
[22]
Mccabe SM, Zhao N. The potential roles of blood-brain barrier and blood-cerebrospinal fluid barrier in maintaining brain manganese homeostasis. Nutrients 2021; 13(6): 1833.
[http://dx.doi.org/10.3390/nu13061833]
[23]
Nagelhus EA, Ottersen OP. Physiological roles of aquaporin-4 in brain. Physiol Rev 2013; 93(4): 1543-62.
[http://dx.doi.org/10.1152/physrev.00011.2013] [PMID: 24137016]
[24]
Bachhuber F, Tumani H. The cerebrospinal fluid and barriers - anatomic and physiologic considerations. Handb Clinical Neurol 2018; pp. 21-32.
[http://dx.doi.org/10.1016/B978-0-12-804279-3.00002-2]
[25]
Brøchner CB, Holst CB, Møllgård K. Outer brain barriers in rat and human development. Front Neurosci 2015; 9: 75.
[http://dx.doi.org/10.3389/fnins.2015.00075] [PMID: 25852456]
[26]
Liu X, Zhang Z, Guo W, Burnstock G, He C, Xiang Z. The superficial glia limitans of mouse and monkey brain and spinal cord. Anat Rec 2013; 296(7): 995-1007.
[http://dx.doi.org/10.1002/ar.22717] [PMID: 23674345]
[27]
Derk J, Jones HE, Como C, Pawlikowski B, Siegenthaler JA, Gilli F. Living on the Edge of the CNS: Meninges cell diversity in health and disease. Front Cell Neurosci 2021; 15: 703944.
[http://dx.doi.org/10.3389/fncel.2021.703944] [PMID: 34276313]
[28]
Redzic ZB, Preston JE, Duncan JA, Chodobski A, Szmydynger-Chodobska J. The choroid plexus-cerebrospinal fluid system: from development to aging. Curr Top Dev Biol 2005; 71: 1-52.
[http://dx.doi.org/10.1016/S0070-2153(05)71001-2] [PMID: 16344101]
[29]
Rabinowicz AL, Carrazana E, Maggio ET. Improvement of intranasal drug delivery with intravail® alkylsaccharide excipient as a mucosal absorption enhancer aiding in the treatment of conditions of the central nervous system. Drugs R D 2021; 21(4): 361-9.
[http://dx.doi.org/10.1007/s40268-021-00360-5] [PMID: 34435339]
[30]
Djupesland PG. Nasal drug delivery devices: characteristics and performance in a clinical perspective-a review. Drug Deliv Transl Res 2013; 3(1): 42-62.
[http://dx.doi.org/10.1007/s13346-012-0108-9] [PMID: 23316447]
[31]
Rossos G, Hadjikakou SK, Kourkoumelis N. Molecular dynamics simulation of 2-benzimidazolyl-urea with DPPC lipid membrane and comparison with a copper(II) complex derivative. Membranes 2021; 11(10): 743.
[http://dx.doi.org/10.3390/membranes11100743] [PMID: 34677508]
[32]
Comparative bioavailability of prochlorperazine edisylate in plasma and brain tissue after intravenous, oral and intranasal administration. 2003. PhD Thesis, Potchefstroom University for Christian Higher Education, 2003.
[33]
Mundlia J, Kumar M. Amardeep. Nasal drug delivery-An overview. Int J Pharm Sci Res 2015; 6(3): 951-60.
[http://dx.doi.org/10.13040/IJPSR.0975-8232.6(3).951-60]
[34]
Bhise S, Yadav A, Avachat A, Malayandi R. Bioavailability of intranasal drug delivery system. Asian J Pharm 2008; 2(4): 201-15.
[http://dx.doi.org/10.4103/0973-8398.45032]
[35]
Proulx ST. Cerebrospinal fluid outflow: a review of the historical and contemporary evidence for arachnoid villi, perineural routes, and dural lymphatics. Cell Mol Life Sci 2021; 78(6): 2429-57.
[http://dx.doi.org/10.1007/s00018-020-03706-5] [PMID: 33427948]
[36]
Simon MJ, Iliff JJ. Regulation of cerebrospinal fluid (CSF) flow in neurodegenerative, neurovascular and neuroinflammatory disease. Biochim Biophys Acta Mol Basis Dis 2016; 1862(3): 442-51.
[http://dx.doi.org/10.1016/j.bbadis.2015.10.014] [PMID: 26499397]
[37]
Pardridge WM. CSF, blood-brain barrier, and brain drug delivery. Expert Opin Drug Deliv 2016; 13(7): 963-75.
[http://dx.doi.org/10.1517/17425247.2016.1171315] [PMID: 27020469]
[38]
Mandula H, Parepally JMR, Feng R, Smith QR. Role of site-specific binding to plasma albumin in drug availability to brain. J Pharmacol Exp Ther 2006; 317(2): 667-75.
[http://dx.doi.org/10.1124/jpet.105.097402] [PMID: 16410405]
[39]
Caterina P, Antonello DP, Chiara G, et al. Pharmacokinetic drug-drug interaction and their implication in clinical management. J Res Med Sci 2013; 18(7): 601-10.
[40]
Raichle ME, Gusnard DA. Appraising the brain’s energy budget. PNAS 2002; 99(16): 10237-9.
[41]
Rink C, Khanna S. Significance of brain tissue oxygenation and the arachidonic acid cascade in stroke. Antioxid Redox Signal 2011; 14(10): 1889-903.
[http://dx.doi.org/10.1089/ars.2010.3474] [PMID: 20673202]
[42]
Fantini S, Sassaroli A, Tgavalekos KT, Kornbluth J, Tgavalekos KT, Kornbluth J. Cerebral blood flow and autoregulation: current measurement techniques and prospects for noninvasive optical methods. Neurophotonics 2016; 3(3): 031411.
[http://dx.doi.org/10.1117/1.NPh.3.3.031411] [PMID: 27403447]
[43]
Zaharchuk G. Theoretical basis of hemodynamic MR imaging techniques to measure cerebral blood volume, cerebral blood flow, and permeability. AJNR Am J Neuroradiol 2007; 28(10): 1850-8.
[http://dx.doi.org/10.3174/ajnr.A0831] [PMID: 17998415]
[44]
Oteng-amoako A. Total retinal blood flow and retinal oxygen saturation in the major retinal vessels of healthy participants PhD Thesis, University of Waterloo, 2013.
[45]
Velocity profile of arterial blood flow and severity of peripheral arterial disease. B.SEd, The University of Georgia, 2009.
[46]
John R. Pappenheimer, Passage of molecules through capillary walls. J Physiol Org 2022; 33: 387-423.
[47]
M.G. Norah Kairys. Joe M Das, Acute Subarachnoid Hemorrhage, NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health, 2022.
[48]
Kishimoto S, Maruhashi T, Kajikawa M, et al. Hematocrit, hemoglobin and red blood cells are associated with vascular function and vascular structure in men. Sci Rep 2020; 10(1): 11467.
[http://dx.doi.org/10.1038/s41598-020-68319-1] [PMID: 32651430]
[49]
Pourcyrous M, Chilakala S, Elabiad MT, Parfenova H, Leffler CW. Does prolonged severe hypercapnia interfere with normal cerebrovascular function in piglets? Pediatr Res 2018; 84(2): 290-5.
[http://dx.doi.org/10.1038/s41390-018-0061-5] [PMID: 29907849]
[50]
Kisler K, Nelson AR, Montagne A, Zlokovic BV. Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease. Nat Rev Neurosci 2017; 18(7): 419-34.
[http://dx.doi.org/10.1038/nrn.2017.48] [PMID: 28515434]
[51]
Hashem M. A multimodal Near-Infrared and MRI technique to assess cerebral metabolic changes in mouse models of neurological diseases. 2022. PhD Thesis, University of Calgary, 2022.
[52]
Bor-Seng-Shu E, Kita WS, Figueiredo EG, et al. Cerebral hemodynamics : concepts of clinical importance. Arq Neuropsiquiatr 2012; 70(5): 352-6.
[http://dx.doi.org/10.1590/s0004-282x2012000500010] [PMID: 22618788]
[53]
Hervé F, Ghinea N, Scherrmann JM. CNS delivery via adsorptive transcytosis. AAPS J 2008; 10(3): 455-72.
[http://dx.doi.org/10.1208/s12248-008-9055-2] [PMID: 18726697]
[54]
Pharmacokinetics of CNS Penetration. Blood-brain barrier in drug discovery optimizing brain exposure of CNS Drugs and Minimizing Brain Side. Wiley 2015.
[55]
McGregor JM, Doolittle ND, Youngers E, Bell SD, Neuwelt EA. Pharmacokinetics of Drug Delivery Past the Blood-Brain Barrier. Elsevier Inc. 2019.
[http://dx.doi.org/10.1016/B978-0-12-813997-4.00004-9]
[56]
Naqvi S, Panghal A, Flora SJS. Nanotechnology: A promising approach for delivery of neuroprotective drugs. Front Neurosci 2020; 14: 494.
[http://dx.doi.org/10.3389/fnins.2020.00494] [PMID: 32581676]
[57]
Laksitorini M, Prasasty VD, Kiptoo PK, Siahaan TJ. Pathways and progress in improving drug delivery through the intestinal mucosa and blood-brain barriers. Ther Deliv 2014; 5(10): 1143-63.
[http://dx.doi.org/10.4155/tde.14.67] [PMID: 25418271]
[58]
Upadhyay RK. Transendothelial transport and its role in therapeutics. Int Sch Res Notices 2014; 2014: 309404.
[http://dx.doi.org/10.1155/2014/309404]
[59]
de Lange ECM. The mastermind approach to CNS drug therapy: translational prediction of human brain distribution, target site kinetics, and therapeutic effects. Fluids Barriers CNS 2013; 10(1): 12.
[http://dx.doi.org/10.1186/2045-8118-10-12] [PMID: 23432852]
[60]
Jahn MR, Nawroth T, Fütterer S, Wolfrum U, Kolb U, Langguth P. Iron oxide/hydroxide nanoparticles with negatively charged shells show increased uptake in Caco-2 cells. Mol Pharm 2012; 9(6): 1628-37.
[http://dx.doi.org/10.1021/mp200628u] [PMID: 22587679]
[61]
Lo W, Potschka H. Blood-brain barrier active efflux transporters: ATP-binding cassette gene family. NeuroRx J Am Soc Exp Neurother 2005; 2: 86-98.
[62]
Yu C. ABC Transporters in multidrug resistance and pharmacokinetics, and strategies for drug development. Curr Pharm Des 2014; 20(5): 793-807.
[63]
Maurya SK, Bhattacharya N, Mishra S, et al. Microglia specific drug targeting using natural products for the regulation of redox imbalance in neurodegeneration. Front Pharmacol 2021; 12: 654489.
[http://dx.doi.org/10.3389/fphar.2021.654489] [PMID: 33927630]
[64]
Devanney NA, Stewart AN, Gensel JC. Microglia and macrophage metabolism in CNS injury and disease: The role of immunometabolism in neurodegeneration and neurotrauma. Exp Neurol 2020; 329: 113310. https://doi.org/https://doi.org/10.1016/j.expneurol.2020.113310
[http://dx.doi.org/10.1016/j.expneurol.2020.113310] [PMID: 32289316]
[65]
Furihata T, Anzai N. Functional expression of organic ion transporters in astrocytes and their potential as a drug target in the treatment of central nervous system diseases. Biol Pharm Bull 2017; 40(8): 1153-60.
[http://dx.doi.org/10.1248/bpb.b17-00076] [PMID: 28768996]
[66]
Wang S, Wang B, Shang D, Zhang K, Yan X, Zhang X. Ion channel dysfunction in astrocytes in neurodegenerative diseases. Front Physiol 2022; 13: 814285.
[http://dx.doi.org/10.3389/fphys.2022.814285] [PMID: 35222082]
[67]
Lee HG, Wheeler MA, Quintana FJ. Function and therapeutic value of astrocytes in neurological diseases. Nat Rev Drug Discov 2022; 21(5): 339-58.
[http://dx.doi.org/10.1038/s41573-022-00390-x] [PMID: 35173313]
[68]
Nance E, Pun SH, Saigal R, Sellers DL. Drug delivery to the central nervous system. Nat Rev Mater 2021; 7(4): 314-31.
[http://dx.doi.org/10.1038/s41578-021-00394-w]
[69]
Zhang F, Lin YA, Kannan S, Kannan RM. Targeting specific cells in the brain with nanomedicines for CNS therapies. J Control Release 2016; 240: 212-26.
[http://dx.doi.org/10.1016/j.jconrel.2015.12.013] [PMID: 26686078]
[70]
Güemes A, Georgiou P. Review of the role of the nervous system in glucose homoeostasis and future perspectives towards the management of diabetes. Bioelectron Med 2018; 4(1): 9.
[http://dx.doi.org/10.1186/s42234-018-0009-4] [PMID: 32232085]
[71]
Casavant MJ. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. McGraw Hill 2006.
[http://dx.doi.org/10.1001/jama.288.16.2052]
[72]
Avdeef A. Physicochemical profiling (solubility, permeability and charge state). Curr Top Med Chem 2001; 1(4): 277-351.
[http://dx.doi.org/10.2174/1568026013395100] [PMID: 11899112]
[73]
Riley RJ, Parker AJ, Trigg S, Manners CN. Development of a generalized, quantitative physicochemical model of CYP3A4 inhibition for use in early drug discovery. Pharm Res 2001; 18(5): 652-5.
[http://dx.doi.org/10.1023/A:1011085411050] [PMID: 11465421]
[74]
Mannhold R. The impact of lipophilicity in drug research: a case report on beta-blockers. Mini Rev Med Chem 2005; 5(2): 197-205.
[http://dx.doi.org/10.2174/1389557053402701] [PMID: 15720289]
[75]
Bergström CAS. In silico predictions of drug solubility and permeability: two rate-limiting barriers to oral drug absorption. Basic Clin Pharmacol Toxicol 2005; 96(3): 156-61.
[http://dx.doi.org/10.1111/j.1742-7843.2005.pto960303.x] [PMID: 15733209]
[76]
Mohammed AS. Drug metabolism and pharmacokinetics, the blood-brain barrier, and central nervous system drug discovery. Am Soc Exp Neurother 2005; 2: 554-71.
[77]
Bickel U. How to measure drug transport across the blood-brain barrier. NeuroRx 2005; 2(1): 15-26.
[http://dx.doi.org/10.1602/neurorx.2.1.15] [PMID: 15717054]
[78]
Ohno K, Pettigrew KD, Rapoport SI. Lower limits of cerebrovascular permeability to nonelectrolytes in the conscious rat. Am J Physiol Heart Circ Physiol 1978; 235(3): H299-307.
[http://dx.doi.org/10.1152/ajpheart.1978.235.3.H299] [PMID: 696840]
[79]
Crone C. The permeability of capillaries in various organs as determined by use of the ‘indicator diffusion’ method. Acta Physiol Scand 1963; 58(4): 292-305.
[http://dx.doi.org/10.1111/j.1748-1716.1963.tb02652.x] [PMID: 14078649]
[80]
Kodaira H, Kusuhara H, Fuse E, Ushiki J, Sugiyama Y. Quantitative investigation of the brain-to-cerebrospinal fluid unbound drug concentration ratio under steady-state conditions in rats using a pharmacokinetic model and scaling factors for active efflux transporters. Drug Metab Dispos 2014; 42(6): 983-9.
[http://dx.doi.org/10.1124/dmd.113.056606] [PMID: 24644297]
[81]
Rowland M, Tozer TN. Clinical pharmacokinetics: concepts and applications. J Pharm Sci 1981; 70: 973-4.
[82]
Stocco MR, Tyndale RF. Cytochrome P450 enzymes and metabolism of drugs and neurotoxins within the mammalian brain. In: Academic Press. 2022; pp. 73-106.
[83]
Haduch A, Daniel WA. The engagement of brain cytochrome P450 in the metabolism of endogenous neuroactive substrates: a possible role in mental disorders. Drug Metab Rev 2018; 50(4): 415-29.
[http://dx.doi.org/10.1080/03602532.2018.1554674] [PMID: 30501426]
[84]
Miksys S, Tyndale R. Cytochrome P450-mediated drug metabolism in the brain. J Psychiatry Neurosci 2013; 38(3): 152-63.
[http://dx.doi.org/10.1503/jpn.120133] [PMID: 23199531]
[85]
Ferguson CS, Tyndale RF. Cytochrome P450 enzymes in the brain: emerging evidence of biological significance. Trends Pharmacol Sci 2011; 32(12): 708-14.
[http://dx.doi.org/10.1016/j.tips.2011.08.005] [PMID: 21975165]
[86]
Wu D, Chen Q, Chen X, Han F, Chen Z, Wang Y. The blood-brain barrier: structure, regulation, and drug delivery. Signal Transduct Target Ther 2023; 8(1): 217.
[http://dx.doi.org/10.1038/s41392-023-01481-w] [PMID: 37231000]
[87]
Pardridge WM. Drug transport across the blood-brain barrier. J Cereb Blood Flow Metab 2012; 32(11): 1959-72.
[http://dx.doi.org/10.1038/jcbfm.2012.126] [PMID: 22929442]
[88]
Minn A, Ghersi-Egea JF, Perrin R, Leininger B, Siest G. Drug metabolizing enzymes in the brain and cerebral microvessels. Brain Res Brain Res Rev 1991; 16(1): 65-82.
[http://dx.doi.org/10.1016/0165-0173(91)90020-9] [PMID: 1907518]
[89]
Di L. The role of drug metabolizing enzymes in clearance. Expert Opin Drug Metab Toxicol 2014; 10(3): 379-93.
[http://dx.doi.org/10.1517/17425255.2014.876006] [PMID: 24392841]
[90]
Agarwal V, Kommaddi RP, Valli K, et al. Drug metabolism in human brain: high levels of cytochrome P4503A43 in brain and metabolism of anti-anxiety drug alprazolam to its active metabolite. PLoS One 2008; 3(6): e2337.
[http://dx.doi.org/10.1371/journal.pone.0002337] [PMID: 18545703]
[91]
Zhao M, Ma J, Li M, et al. Cytochrome P450 enzymes and drug metabolism in humans. Int J Mol Sci 2021; 22(23): 12808.
[http://dx.doi.org/10.3390/ijms222312808] [PMID: 34884615]
[92]
Ghosh C, Puvenna V, Gonzalez-Martinez J, Janigro D, Marchi N. Blood-brain barrier P450 enzymes and multidrug transporters in drug resistance: a synergistic role in neurological diseases. Curr Drug Metab 2011; 12(8): 742-9.
[http://dx.doi.org/10.2174/138920011798357051] [PMID: 21568937]
[93]
Sun H, Dai H, Shaik N, Elmquist WF. Drug efflux transporters in the CNS. Adv Drug Deliv Rev 2003; 55(1): 83-105.
[http://dx.doi.org/10.1016/S0169-409X(02)00172-2] [PMID: 12535575]
[94]
Taylor EM. The impact of efflux transporters in the brain on the development of drugs for CNS disorders. Clin Pharmacokinet 2002; 41(2): 81-92.
[http://dx.doi.org/10.2165/00003088-200241020-00001] [PMID: 11888329]
[95]
Löscher W, Potschka H. Drug resistance in brain diseases and the role of drug efflux transporters. Nat Rev Neurosci 2005; 6(8): 591-602.
[http://dx.doi.org/10.1038/nrn1728] [PMID: 16025095]
[96]
Zhang Z, Tang W. Drug metabolism in drug discovery and development. Acta Pharm Sin B 2018; 8(5): 721-32.
[http://dx.doi.org/10.1016/j.apsb.2018.04.003] [PMID: 30245961]
[97]
de Lange ECM. Utility of CSF in translational neuroscience. J Pharmacokinet Pharmacodyn 2013; 40(3): 315-26.
[http://dx.doi.org/10.1007/s10928-013-9301-9] [PMID: 23400635]
[98]
Hovd MH, Mariussen E, Uggerud H, et al. Population pharmacokinetic modeling of CSF to blood clearance: prospective tracer study of 161 patients under work-up for CSF disorders. Fluids Barriers CNS 2022; 19(1): 55.
[http://dx.doi.org/10.1186/s12987-022-00352-w] [PMID: 35778719]
[99]
Singh AK, Gothwal A, Rani S, et al. Dendrimer donepezil conjugates for improved brain delivery and better in vivo pharmacokinetics. ACS Omega 2019; 4(3): 4519-29.
[http://dx.doi.org/10.1021/acsomega.8b03445]
[100]
Sharma B, Luhach K, Kulkarni GT. In vitro and in vivo models of BBB to evaluate brain targeting drug delivery. Elsevier Ltd. 2018.
[http://dx.doi.org/10.1016/B978-0-12-814001-7.00004-4]
[101]
Chaulagain B, Gothwal A, Lamptey RNL, et al. Experimental models of in vitro blood-brain barrier for cns drug delivery: An evolutionary perspective. Int J Mol Sci 2023; 24(3): 2710.
[http://dx.doi.org/10.3390/ijms24032710] [PMID: 36769032]
[102]
Árpád K, Applicability of a blood-brain barrier specific artificial membrane permeability assay at the early stage of natural product-based CNS drug discovery. J Nat Prod 2013; 76: 655-63.
[103]
Dhakar A, Maurya SD, Tilak VK, et al. A review on factors affecting the design of nasal drug delivery system. Int J Drug Deliv 2011; 3: 194-208.
[http://dx.doi.org/10.5138/ijdd.v3i2.214]
[104]
Deli MA. Biochimica et Biophysica Acta Potential use of tight junction modulators to reversibly open membranous barriers and improve drug delivery BBA - Biomembr 2009; 1788: 892-.
[http://dx.doi.org/10.1016/j.bbamem.2008.09.016]
[105]
Din F, Aman W, Ullah I, et al. Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors. Int J Nanomedicine 2017; 12: 7291-309.
[http://dx.doi.org/10.2147/IJN.S146315]
[106]
Bayón-Cordero L, Alkorta I, Arana L. Application of solid lipid nanoparticles to improve the efficiency of anticancer drugs. Nanomaterials (Basel) 2019; 9(3): 474.
[http://dx.doi.org/10.3390/nano9030474] [PMID: 30909401]
[107]
Haque S, Md S, Sahni JK, Ali J, Baboota S. Development and evaluation of brain targeted intranasal alginate nanoparticles for treatment of depression. J Psychiatr Res 2014; 48(1): 1-12.
[http://dx.doi.org/10.1016/j.jpsychires.2013.10.011] [PMID: 24231512]
[108]
Sadegh Malvajerd S, Azadi A, Izadi Z, et al. Brain delivery of curcumin using solid lipid nanoparticles and nanostructured lipid carriers: Preparation, optimization, and pharmacokinetic evaluation. ACS Chem Neurosci 2019; 10(1): 728-39.
[http://dx.doi.org/10.1021/acschemneuro.8b00510] [PMID: 30335941]
[109]
Yasir M, Sara UVS. Solid lipid nanoparticles for nose to brain delivery of haloperidol: in vitro drug release and pharmacokinetics evaluation. Acta Pharm Sin B 2014; 4(6): 454-63.
[http://dx.doi.org/10.1016/j.apsb.2014.10.005] [PMID: 26579417]
[110]
Fatouh A, Elshafeey A, Abdelbary A. Intranasal agomelatine solid lipid nanoparticles to enhance brain delivery: formulation, optimization and in vivo pharmacokinetics. Drug Des Devel Ther 2017; 11: 1815-25.
[http://dx.doi.org/10.2147/DDDT.S102500] [PMID: 28684900]
[111]
Jazuli I, Annu B, Nabi B, et al. Optimization of nanostructured lipid carriers of lurasidone hydrochloride using box-behnken design for brain targeting: In vitro and in vivo studies. J Pharm Sci 2019; 108(9): 3082-90.
[http://dx.doi.org/10.1016/j.xphs.2019.05.001] [PMID: 31077685]
[112]
Patel RJ, Parikh RH. Intranasal delivery of topiramate nanoemulsion: Pharmacodynamic, pharmacokinetic and brain uptake studies. Int J Pharm 2020; 585: 119486.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119486] [PMID: 32502686]
[113]
Abdou EM, Kandil SM, Miniawy HMFE. Brain targeting efficiency of antimigrain drug loaded mucoadhesive intranasal nanoemulsion. Int J Pharm 2017; 529(1-2): 667-77.
[http://dx.doi.org/10.1016/j.ijpharm.2017.07.030] [PMID: 28729175]
[114]
Harun S, Amin Nordin S, Abd Gani SS, Shamsuddin AF, Basri M, Bin Basri H. Development of nanoemulsion for efficient brain parenteral delivery of cefuroxime: designs, characterizations, and pharmacokinetics. Int J Nanomedicine 2018; 13: 2571-84.
[http://dx.doi.org/10.2147/IJN.S151788] [PMID: 29731632]
[115]
Ahmed TA, El-Say KM, Ahmed OAA, Aljaeid BM. Superiority of TPGS-loaded micelles in the brain delivery of vinpocetine via administration of thermosensitive intranasal gel. Int J Nanomedicine 2019; 14: 5555-67.
[http://dx.doi.org/10.2147/IJN.S213086] [PMID: 31413562]
[116]
Sharma AK, Gupta L, Sahu H, et al. Chitosan engineered PAMAM dendrimers as nanoconstructs for the enhanced anti-cancer potential and improved in vivo brain pharmacokinetics of temozolomide. Pharm Res 2018; 35(1): 9.
[http://dx.doi.org/10.1007/s11095-017-2324-y] [PMID: 29294212]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy