Protein drug binding

Drug Protein Binding (%) Half-Life (hours) Active Metabolite(s)... 

Sebille, B. Methods of drug protein binding determinations. Fund. Clin. Pharmacol. 1990, 4[Suppl. 2], 151s-161s. 

Drug-protein binding is the reversible interaction of drugs v/ith different proteins in plasma. Albumin is not the exclusive protein involved. Drugs bind to specific sites on the protein. 

MHA Busch, LB Carels, HFM Boelens, JC Kraak, H Poppe. Comparison of five methods for the study of drug-protein binding in affinity capillary electrophoresis. J Chromatogr A 777 311-328, 1997. 

A Shibukawa, Y Kuroda, T Nakagawa. High-performance frontal analysis for drug-protein binding study. J. Pharm. Biomed. Anal. 18(6) 1047-1055 (1999). 

J Oravcova, B Bohs, W Lindner. Drug-protein binding studies. New trends in analytical and experimental methodology. J Chromatogr B 677 1—28, 1996. 

CGE) and capillary electrochromatography (CEC) are also not covered. The authors took care to include all relevant references. Nevertheless, some noteworthy investigations may have been overlooked. Readers more interested in this specific field of ACE are therefore referred to recent reviews (1-7) that deal especially with different aspects of drug-protein binding interactions. 

Fig. 1 Schematic representation of the experimental setups of the mobility-shift method and the Hummel-Dreyer method (A) the vacancy peak method and the vacancy affinity capillary electrophoresis method (B) the equilibrium-mixture method and the frontal analysis method (C) for drug-protein binding analysis. drug protein gg drug-protein complex Q buffer. (Reprinted with permission from Ref. 38. Copyright 1992 Elsevier Science.)...

H Shiono, A Shibukawa, Y Kuroda, T Nakagawa. Effect of sialic acid residues of human ay-acid glycoprotein on stereoselectivity in basic drug-protein binding. Chirality 9 291-296, 1997. 

Singh, S.S. and Mehta, J. (2006) Measurement of drug-protein binding by immobilized human serum albumin-HPLC and comparison with ultrafiltration. Journal of Chromatography B, 834, 108-116. 

Widely used in bioanalysis for measuring small amounts of drug and for studying drug-protein binding. 

Determination of partition coefficients and pAa values of drugs and of drug protein binding. 

Vanholder, R., De Smet, R., and Ringoir, S. (1993) Factors influencing drug protein binding in patients with end-stage renal failure. Eur J Clin Pharmacol 44 S17-S21. 

Drug Protein binding Haif-iife (hours) Relations to cytochrome P450 (CYP) system other key features... 

Sometimes the easiest way to destroy drug-protein binding is to dilute the sample with a physiological saline solution. For instance, for isoxazolyl penicillins with a binding percentage of over 95%, dilution with 9 volumes of 0.9% sodium chloride solution can be sufficient (9). Alternative widely used techniques are based on either protein denaturation or enzymatic/chemical hydrolysis of the drug-protein complexes (10-12). 

TABLE 5.3 Results from an LC/MS-based drug-protein binding screen using HPLC columns containing immobilized human serum albumin to determine the relative binding of drugs... 

Tiller, P. R. Mutton, I. M. Lane, S. J. Bevan, C. D. 1995. Immobilized human serum albumin liquid chromatography/mass spectrometry as a method of determining drug-protein binding. Rapid Commun. Mass Spectrom., 9,261-263. 

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