COMPOUNDS THAT BIND TO PLASMA PROTEINS IN HUMANS. SIGNIFICANCE IN THERAPY AND METHODS FOR QUANTIFICATION OF A FREE FRACTION
DOI:
https://doi.org/10.56782/pps.76Keywords:
unbound fraction, drug, albumin, plasma proteins, ultrafiltration, equilibrium dialysisAbstract
Many endogenous and exogenous substances are able to bind to plasma proteins, mainly to human serum albumin and α-1-acid glycoprotein. In the bloodstream, these substances are present both in a free and in a protein-bound form. The protein has on its surface binding sites, specific for a given compound, which differ in size, shape and affinity. Binding is mediated by hydrophobic, van der Waals and/or electrostatic interactions. The extent to which compounds bind to plasma proteins depends on a number of different factors, including the presence of inflammation, kidney and liver diseases, and age. Only the free fraction is biologically active and is able to cross biological barriers. Therefore, methods of measuring the free plasma concentration of compounds are crucial. The most commonly used method is equilibrium dialysis, which is considered to be the reference method. Other methods include ultrafiltration, ultracentrifugation, microdialysis, microextraction, high-performance frontal analysis and cloud point extraction.
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References
Kratz F., Elsadek B. Clinical impact of serum proteins on drug delivery. Journal of Controlled Release, 2012, 161(2), 429-445. DOI: https://doi.org/10.1016/j.jconrel.2011.11.028
Fan J., de Lannoy I. A. M.: Pharmacokinetics. Biochemical Pharmacology, 2014, 87, 93-120. DOI: https://doi.org/10.1016/j.bcp.2013.09.007
Dasgupta A., Usefulness of monitoring free (unbound) concentrations of therapeutic drugs in patient management. Clinica Chimica Acta, 2007, 377(1-2), 1-13. DOI: https://doi.org/10.1016/j.cca.2006.08.026
Riccordi K., Cawley S., Yates P. D., Chang C., Funk C., Niosi M., Lin J., Di L. Plasma Protein Binding of Challenging Compounds. Journal of Pharmaceutical Sciences, 2015, 104 (8), 2627-2636. DOI: https://doi.org/10.1002/jps.24506
Valerio C., Theocharidou E., Davenport A., Agarwal B. Human albumin solution for patients with cirrhosis and acute on chronic liver failure: Beyond simple volume expansion. World Journal of Hepatology, 2016, 8(7), 345-354. DOI: https://doi.org/10.4254/wjh.v8.i7.345
Yang F., Zhang Y., Liang H. Interactive association of drugs binding to human serum albumin. International Journal of Molecular Sciences, 2014, 15(3), 3580-3595. DOI: https://doi.org/10.3390/ijms15033580
Stegmayr B., New insight in impaired binding capacity for albumin in uraemic patients. Acta Physiologica, 2015, 215(1), 5-8. DOI: https://doi.org/10.1111/apha.12546
Simonsen K., Rode A., Nicoll A., Villadsen G., Espelund U., Lim L., Angus P., Arachchi N., Vilstrup H., Nexo E., Grønbæk H. Vitamin B12 and its binding proteins in hepatocellular carcinoma and chronic liver diseases. Scandinavian Journal of Gastroenterology, 2014, 49(9), 1096-1102. DOI: https://doi.org/10.3109/00365521.2014.921325
Tran M.T., Stürup S., Lambert I. H., Gammelgaard B., Furger E., Alberto R. Cellular uptake of metallated cobalamins. Metallomics, 2016, 8, 298-304. DOI: https://doi.org/10.1039/C5MT00272A
Gkouvatsos K., Papanikolaou G., Pantopoulos K. Regulation of iron transport and the role of transferrin. Biochimica et Biophysica Acta (BBA) - General Subjects, 2012, 1820(3), 188-202. DOI: https://doi.org/10.1016/j.bbagen.2011.10.013
Pappa T., Ferrara A. M., Refetoff S. Inherited defects of thyroxine-binding proteins. Best Practice & Research Clinical Endocrinology & Metabolism, 2015, 29(5), 735-747. DOI: https://doi.org/10.1016/j.beem.2015.09.002
Zhivkova Z.D., Studies on drug-human serum albumin binding: the current state of the matter. Current Pharmaceutical Design, 2015, 21(14), 1817-1830. DOI: https://doi.org/10.2174/1381612821666150302113710
Senis Y., Garcia-Alonso A. Platelet Proteomics: Principles, Analysis, and Applications, WILEY, Canada, 2011. DOI: https://doi.org/10.1002/9780470940297
Andersen M.M., Leucocyte-Associated Plasma Proteins. Scandinavian Journal of Immunology, 1982, 15 (4), 399-407. DOI: https://doi.org/10.1111/j.1365-3083.1982.tb00664.x
Lambrinidis G., Vallianatou T., Tsantili-Kakoulidou A. In vitro, in silico and integrated strategies for the estimation of plasma protein binding. A review. Advanced Drug Delivery Reviews, 2015, 86, 27-45. DOI: https://doi.org/10.1016/j.addr.2015.03.011
Bohnert T., Gan L. S. Plasma protein binding: From discovery to development. Journal of Pharmaceutical Sciences, 2013, 102, 2953-2994. DOI: https://doi.org/10.1002/jps.23614
Lee P., Wu X. Review: modifications of human serum albumin and their binding effect. Current pharmaceutical design, 2015, 21(14), 1862-1865. DOI: https://doi.org/10.2174/1381612821666150302115025
Anraku M., Shintomo R., Taguchi K., Kragh-Hansen U., Kai T., Maruyama T., Otagiri M. Amino acids of importance for the antioxidant activity of human serum albumin as revealed by recombinant mutants and genetic variants. Life Sciences, 2015, 134, 36-41. DOI: https://doi.org/10.1016/j.lfs.2015.05.010
Roche M., Rondeau P., Singh N. R., Tarnus E., Bourdon E. The antioxidant properties of serum albumin. Febs Letters, 2008, 582(13), 1783-1787. DOI: https://doi.org/10.1016/j.febslet.2008.04.057
Larsen M. T., Kuhlmann M., Hvam M. L., Howard K. A. Albumin-based drug delivery: harnessing nature to cure disease. Molecullar and Cellular Therapies, 2016, 4, 3. DOI: https://doi.org/10.1186/s40591-016-0048-8
Zhu L., Yang F., Chen L., Meehan E. J., Huang M. A new drug binding subsite on human serum albumin and drug-drug interaction studied by X-ray crystallography. Journal of Structural Biology, 2008, 162(1), 40-49. DOI: https://doi.org/10.1016/j.jsb.2007.12.004
Kopecký V. Jr., Ettrich R., Hofbauerová K., Baumruk V. Structure of human alpha1-acid glycoprotein and its high-affinity binding site. Biochemical and Biophysical Research Communications, 2003, 300(1), 41-46. DOI: https://doi.org/10.1016/S0006-291X(02)02765-1
Solomon E. P., Berg L., Martin D. Biologia, Warszawa, Multico, 2013.
Smith D. A., Di L., Kerns E. H. The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery. Nature Reviews Drug Discovery, 2010, 9, 929-939. DOI: https://doi.org/10.1038/nrd3287
Peltenburg H., Bosman I. J., Hermens J. L. M. Sensitive determination of plasma protein binding of cationic drugs using mixed-mode solid-phase microextraction. Journal of Pharmaceutical and Biomedical Analysis, 2015, 115, 534-542. DOI: https://doi.org/10.1016/j.jpba.2015.08.002
Zeitlinger M. A., Derendorf H., Mouton J. W., Cars O., Craig W. A., Andes D., Theuretzbacher U. Protein Binding: Do We Ever Learn? Antimicrobial Agents and chemotherapy, 2011, 55(7), 3067-3074. DOI: https://doi.org/10.1128/AAC.01433-10
Yamasaki K., Maruyama T., Kragh-Hansen U., Otagiri M. Characterization of site I on human serum albumin: concept about the structure of a drug binding site. Biochim Biophys Acta, 1996, 1295 (2), 147-157. DOI: https://doi.org/10.1016/0167-4838(96)00013-1
Dawidowicz A. L., Kobielski M., Pieniadz J. Anomalous relationship between free drug fraction and its total concentration in drug–protein systems: I. Investigation of propofol binding in model HSA solution. European Journal of Pharmaceutical Sciences, 2008, 34(1), 30-36. DOI: https://doi.org/10.1016/j.ejps.2008.02.004
Zhang F., Xue J., Shao J., Jia L. Compilation of 222 drugs' plasma protein binding data and guidance for study designs. Drug Discovery Today, 2012, 17(9-10), 475-485. DOI: https://doi.org/10.1016/j.drudis.2011.12.018
Ghuman J., Zunszain P. A., Petitpas I., Bhattacharya A. A., Otagiri M., Curry S. Structural basis of the drug-binding specificity of human serum albumin. Journal of Molecular Biology, 2005, 353(1), 38-52. DOI: https://doi.org/10.1016/j.jmb.2005.07.075
Trynda-Lemiesz L., Wiglusz K., Mucha I. The role of albumin in the diagnostics. Binding of ions and metal complexes. Wiadomości Chemiczne, 2010, 64(1-2), 81-104.
Cui Y. F., Bai G. Y., Li C. G., Ye C. H., Liu M. L. Analysis of competitive binding of ligands to human serum albumin using NMR relaxation measurements. Journal of Pharmaceutical and Biomedical Analysis, 2004, 34(2), 247-254. DOI: https://doi.org/10.1016/S0731-7085(03)00579-X
Zsila F., Bikadi Z., Malik D., Hari P., Pechan I., Berces A., Hazai E. Evaluation of drug–human serum albumin binding interactions with support vector machine aided online automated docking. Bioinformatics, 2011, 27(13), 1806-1813. DOI: https://doi.org/10.1093/bioinformatics/btr284
Shen Q., Wang L., Zhou H., Jiang H.D., Yu L. S., Zeng S. Stereoselective binding of chiral drugs to plasma proteins. Acta Pharmacologica Sinica, 2013, 34(8), 998-1006. DOI: https://doi.org/10.1038/aps.2013.78
Arroyo V., García-Martinez R., Salvatella X. Human serum albumin, systemic inflammation, and cirrhosis. Journal of hepatology, 2014, 61(2), 396-407. DOI: https://doi.org/10.1016/j.jhep.2014.04.012
Merlot A. M., Kalinowski D. S., Richardson D. R. Unraveling the mysteries of serum albumin-more than just a serum protein. Froniers in physiology, 2014, 5, 299. DOI: https://doi.org/10.3389/fphys.2014.00299
Novotná P., Urbanová M. Bilirubin, model membranes and serum albumin interaction: The influence of fatty acids. Biochimica et biophysica acta, 2015, 1848 (6), 1331-1340. DOI: https://doi.org/10.1016/j.bbamem.2015.02.026
van der Vusse G.J., Albumin as fatty acid transporter. Drug metabolism and pharmacokinetics, 2009, 24(4), 300-307. DOI: https://doi.org/10.2133/dmpk.24.300
Vanholder R., Van Laecke S., Glorieux G. What is new in uremic toxicity? Pediatr Nephrol, 2008, 23(8), 1211-1221. DOI: https://doi.org/10.1007/s00467-008-0762-9
Evenepoel P., Meijers B. K., Bammens B. R., Verbeke K. Uremic toxins originating from colonic microbial metabolism. Kidney International. Supplement, 2009, 114, 12-19. DOI: https://doi.org/10.1038/ki.2009.402
Watanabe H., Noguchi T., Miyamoto Y., Kadowaki D., Kotani S., Nakajima M., Miyamura S., Ishima Y., Otagiri M., Maruyama T. Interaction between two sulfate-conjugated uremic toxins, p-cresyl sulfate and indoxyl sulfate, during binding with human serum albumin. Drug Metabolism & Disposition, 2012, 40(7), 1423-1428. DOI: https://doi.org/10.1124/dmd.112.045617
Devine E., Krieter D. H., Rüth M., Jankovski J., Lemke H. D. Binding affinity and capacity for the uremic toxin indoxyl sulfate. Toxins, 2014, 6(2), 416-429. DOI: https://doi.org/10.3390/toxins6020416
Nicholson J. P., Wolmarans M. R., Park G. R. The role of albumin in critical illness. British Journal of Anaesthesia, 2000, 85(4), 599-610. DOI: https://doi.org/10.1093/bja/85.4.599
Francis G.L., Albumin and mammalian cell culture: implications for biotechnology applications. Cytotechnology, 2010, 62(1), 1-16. DOI: https://doi.org/10.1007/s10616-010-9263-3
Maciążek-Jurczyk M., Szkudlarek-Haśnik A., Siek D., Chłosta M., FarugaK., Moskała W., Sułkowska A. Binding of ketoprofen to plasma protein in inflammatory states. Annales Academiae medicae silesiensis, 2002, 66(3), 27-33.
Załuska W., Water as a uraemic toxin? Forum Nefrologiczne, 2010, 3(1), 12-17.
Viaene L., Annaert P., de Loor H., Poesen R., Evenepoel P., Meijers B. Albumin is the main plasma binding protein for indoxyl sulfate and p-cresyl sulfate. Biopharmaceutics & Drug Disposition, 2013, 34(3), 165-175. DOI: https://doi.org/10.1002/bdd.1834
Otagiri M., A molecular functional study on the interactions of drugs with plasma proteins. Drug Metabolism and Pharmacokinetics, 2005, 20(5), 309-323. DOI: https://doi.org/10.2133/dmpk.20.309
Clarke D. F., Wong R. J., Wenning L., Stevenson D. K., Mirochnick M. Raltegravir in vitro effect on bilirubin binding. The pediatric infectious disease journal, 2013, 32(9), 978-980. DOI: https://doi.org/10.1097/INF.0b013e31829044a8
Bai G., Cui Y., Yang Y., Ye C., Liu M. A competitive low-affinity binding model for determining the mutual and specific sites of two ligands on protein. Journal of Pharmaceutical and Biomedical Analysis, 2005, 38(4), 588-593. DOI: https://doi.org/10.1016/j.jpba.2004.12.037
Ascenzi P., Fanalib G., Fasanob M., Pallottinic V., Trezzac V. Clinical relevance of drug binding to plasma proteins. Journal of Molecular Structure, 2014, 1077(6), 4-13. DOI: https://doi.org/10.1016/j.molstruc.2013.09.053
Stegmayr B., Uremic toxins and lipases in haemodialysis: a process of repeated metabolic starvation. Toxins (Basel), 2014, 6(5), 1505-1511. DOI: https://doi.org/10.3390/toxins6051505
Curran R. E., Claxton C. R., Hutchison L., Harradine P. J., Martin I. J., Littlewood P. Control and Measurement of Plasma pH in Equilibrium Dialysis: Influence on Drug Plasma Protein Binding. Drug Metabolism & Disposition, 2011, 39(3), 551-557. DOI: https://doi.org/10.1124/dmd.110.036988
Fogh-Andersen N., Bjerrum P. J., Siggaard-Andersen O. Ionic binding, net charge, and Donnan effect of human serum albumin as a function of pH. Clinical Chemistry, 1993, 39(1), 140-152. DOI: https://doi.org/10.1093/clinchem/39.1.48
Bolton G. R., Boesch A.W., Basha J., Lacasse D. P., Kelley B. D., Acharya H. Effect of protein and solution properties on the donnan effect during the ultrafiltration of proteins. Biotechnology Progress, 2011, 27(1), 140-152. DOI: https://doi.org/10.1002/btpr.523
Gonzalez D., Schmidt S., Derendorf H. Importance of Relating Efficacy Measures to Unbound Drug Concentrations for Anti-Infective Agents. Clinical Microbiology Reviews, 2013, 26(2), 274-288. DOI: https://doi.org/10.1128/CMR.00092-12
Rukhadze M. D., Tsagareli S. K., Sidamonidze N. S., Meyer V. R. Cloud-point extraction for the determination of the free fraction of antiepileptic drugs in blood plasma and saliva. Analytical Biochemistry, 2000, 287(2), 279-283. DOI: https://doi.org/10.1006/abio.2000.4863
Samaddar D., Sen K. Cloud point extraction: A sustainable method of elemental preconcentration and speciation. Journal of Industrial and Engineering Chemistry, 2014, 20(4), 1209-1219 DOI: https://doi.org/10.1016/j.jiec.2013.10.033
Biparva P., Matin A. A. Microextraction Techniques as a Sample Preparation Step for Metal Analysis. Atomic Absorption Spectroscopy, InTech, 2012, 61-88. DOI: https://doi.org/10.5772/30501
Afkham A., Madrakian T., Siampour H. Flame atomic absorption spectrometric determination of trace quantities of cadmium in water samples after cloud point extraction in Triton X-114 without added chelating agents. Journal of Hazardous Materials, 2006, 138(2), 269-272. DOI: https://doi.org/10.1016/j.jhazmat.2006.03.073
Giebułtowicz J., Kojro G., Buś-Kwaśnik K., Rudzki P. J., Marszałek R., Leś A., Wroczyński P. Cloud-point extraction is compatible with liquid chromatography coupled to electrospray ionization mass spectrometry for the determination of bisoprolol in human plasma. Journal of Chromatography A, 2015, 1423, 39-46. DOI: https://doi.org/10.1016/j.chroma.2015.10.076
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