Abstract
Drug protein binding phenomena can lead to some interesting drug—drug interactions when one drug displaces another in the binding site. Studies of protein binding are conducted by several methods including equilibrium dialysis, ultra-filtration and chromatographic methods. Gel filtration is a simple chromatographic method in protein binding studies. Propranolol binds to plasma proteins by 90%–95% in circulation system and other drugs with high protein binding may displace it. In this study protein binding of propranolol has been studied using gel filtration to Bovine Serum Albumin (BSA) alone and in the presence of Acetyl salicylic acid (ASA), Indomethacin and mefenamic acid has been studied using gel filtration method. The results indicated that ASA decreased protein binding of propranolol by 20% to BSA and other drugs did not displace propranolol from the binding site. Therefore, ASA may alter pharmacological effects of propranolol.
Key words: Propranolol, NSAIDs, BSA, Protein Binding, Gel Filtration
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References
- 1.Evans G.H., Nies S.A., Shand D.G. Plasma Binding of Propranolol. J. Pharmac. Exp. Ther. 1973;186:114–122. [PubMed] [Google Scholar]
- 2.Sager G., Odd G., Jacobsen N., Jacobsen S. Variable Binding of Propranolol In Human Serum. Biochemical. Pharmacol. 1979;28:905–911. doi: 10.1016/0006-2952(79)90374-5. [DOI] [PubMed] [Google Scholar]
- 3.Krishnia R., William G.T., Richard E.M. Assay of total and Free Propranolol in Plasma by Liquid Chromatography With Fluorometric Detection. Clin. Chem. 1985;31:131–134. [PubMed] [Google Scholar]
- 4.Sophiunapoulos J.A. Ultrafiltration is Theoritically Equivalent to Equilibrium Dialysis But Much Simpler to Carry out. Arch. Biochem. and Biophys. 1987;187:132–133. doi: 10.1016/0003-9861(78)90015-2. [DOI] [PubMed] [Google Scholar]
- 5.Frans M., Bel P., Rene A., Breackman G., Marc G.B. Binding of Oxprenolol and Propranolol to Serum Albumin and α-Acid glycoprotein in Man And Other Species. Biochem. Pharmacol. 1984;33:2065–2069. doi: 10.1016/0006-2952(84)90575-6. [DOI] [PubMed] [Google Scholar]
- 6.Wood A.J., Feely J. Pharmacokinetic Drug Interaction With Propranolol. Clin. Pharmacol. 1983;8(3):253–262. doi: 10.2165/00003088-198308030-00004. [DOI] [PubMed] [Google Scholar]
- 7.Uma T., Manju B., Sen P., Mahjan P. In vitro interaction between aspirin and propranolol at the plasma protein binding sites. Indian J. Med. Res. 1987;86:95–100. [PubMed] [Google Scholar]
- 8.Houston M.C. Nonsteroidal Anti-inflammatory Drugs And Antihypertensives. Amer. J. Med. 1991;90(Suppl. 5A):42S–47S. doi: 10.1016/0002-9343(91)90485-G. [DOI] [PubMed] [Google Scholar]
- 9.Johnson A.G., Nguyen T.V., Day R.O. Do Nonsteroidal Anti-inflammatory Drugs Affect Blood Pressure? A Meta-analysis. Ann. Intern. Med. 1994;121:289–300. doi: 10.7326/0003-4819-121-4-199408150-00011. [DOI] [PubMed] [Google Scholar]
- 10.Pope J.E., Anderson J.J., Felson D. A Meta-analysis Of The Effects Of Nonsteroidal Anti-inflammatory Drugs On Blood Pressure. Arch. Intrn. Med. 1993;153:477–484. doi: 10.1001/archinte.153.4.477. [DOI] [PubMed] [Google Scholar]
- 11.Kasznicki J., Owczarek A.W. Effects of Indomethacin on Hemodynamic Parameters After Intravenous Administration of Propranolol and Enalaprilate in Rabbits. Polish. J. Pharmacol. 2001;53:487–493. [PubMed] [Google Scholar]
- 12.Amitava D., Timothy G.T. In vitro Displacement of Phenytoin From Protein Binding by Nonsteroidal Antiinflamatory Drugs Tolmetin, Ibuprofen and Naproxen in Normal and Uremic Sera. T.D.M. 1996;18(1):97–99. doi: 10.1097/00007691-199602000-00016. [DOI] [PubMed] [Google Scholar]
- 13.Kamesvar R.K., Mahmou S.A., Thomas P.J., Ashim K.M. Binding of Cosalane A Novel Highly Lipophilic Anti-HIV Agent—to Albumin and Glycoprotein. J. of Pharmaceu. Scien. 2001;90(5):659–666. doi: 10.1002/1520-6017(200105)90:5<659::AID-JPS1022>3.0.CO;2-8. [DOI] [PubMed] [Google Scholar]
- 14.Cooper P.F., Wood G.C. Protein Binding of Small Molecules: New Gel Filtration Method. Pharm. Pharmacol. 1968;20:150s–156s. doi: 10.1111/j.2042-7158.1968.tb09877.x. [DOI] [PubMed] [Google Scholar]
- 15.Wood G.C., Cooper P.F. The Application of Gel Filtration to the Study of Protein Binding of Small Molecules. Chromatog. Rev. 1970;12:88–107. doi: 10.1016/0009-5907(70)80014-X. [DOI] [PubMed] [Google Scholar]
- 16.Sebille B., Zini R., Madjar C.V., Thuaud N., Tillemen J.P. Separation Procedures Used to Reveal and Follow Drug—Protein binding. J. Chromatog. 1990;12(531):51–77. doi: 10.1016/s0378-4347(00)82280-x. [DOI] [PubMed] [Google Scholar]
- 17.Iwamoto, K. and Watanab, J. (1985). Avoidance of First—Pass Metabolism of Propranolol After Rectal Aadministration as a Function of the Absorption Site. Pharmace. Res. 53–54. [DOI] [PubMed]
- 18.Lowry O.H., Rosebrough N.J., Farr A.L., Randell R. Protein measurement with the Folin Phenol reagent. J. Biol. Chem. 1951;243:1331–1332. [PubMed] [Google Scholar]
- 19.Chkrabarti S.K. Cooperativity of Warfarin Binding with SA Induced by Free Fatty Acid Anions. Biochem. Pharmacol. 1978;627:739–743. doi: 10.1016/0006-2952(78)90513-0. [DOI] [PubMed] [Google Scholar]
- 20.Miners J.O. Drug Interaction Involving ASA and SA. Clin. Pharmacoki. 1989;6:372–344. [Google Scholar]
- 21.Jurez O.J., Jung C.H., Flores P.J., Asseff I.L. Clinical evidence of an Interaction Between Imipramine and Acetyl Salisylic Acid on Protein Binding in Depress Patients. Clin. Neuropharmacol. 2002;25(1):32–32. doi: 10.1097/00002826-200201000-00006. [DOI] [PubMed] [Google Scholar]
- 22.Ferry D.G., Caplan N.B., Cubeddu L.X. Interaction Between Antidepressants and α 1-Adrenergic Receptor Antagonists on the Binding to α 1-acid Glycoprotein. J. Pharmaceu. Scein. 1986;75(2):146–149. doi: 10.1002/jps.2600750208. [DOI] [PubMed] [Google Scholar]