Biomaterial Database

Determination of protein binding of gyrase inhibitors by means of continuous ultrafiltration. 1998

G Zlotos, and M Oehlmann, and P Nickel, and U Holzgrabe

Pharmaceutical Institute, University of Bonn, Germany.

In order to characterize the protein binding of a drug, it is necessary to have a method which is close to in vivo conditions and fast in the course of measurement. The continuous ultrafiltration fulfils both requirements for substances with a high extent of protein binding. In this study, 18 gyrase inhibitors in clinical practice, characterized by a lower extent of protein binding, were subjected to the titration procedure of the continuous ultrafiltration using bovine and human serum albumin (BSA, HSA), and human plasma. The results of the continuous ultrafiltration were found to be similar to those obtained by means of the 'classical' discontinuous ultrafiltration using plasma (correlation between continuous and discontinuous ultrafiltration r2 = 0.87). In the cases of pipemidic acid, enoxacin and rufloxacin, the continuous method gave approximately 20% lower degrees of protein binding than the discontinuous procedure, which utilizes plasma having the full range of proteins. It is likely that these drugs bind mainly to other proteins in plasma than HSA. This finding proves that this fast method is worthwhile in the whole range of protein binding.

UI	MeSH Term	Description	Entries
D008956	Models, Chemical	Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.	Chemical Models,Chemical Model,Model, Chemical
D011485	Protein Binding	The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.	Plasma Protein Binding Capacity,Binding, Protein
D001798	Blood Proteins	Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.	Blood Protein,Plasma Protein,Plasma Proteins,Serum Protein,Serum Proteins,Protein, Blood,Protein, Plasma,Protein, Serum,Proteins, Blood,Proteins, Plasma,Proteins, Serum
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014462	Ultrafiltration	The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in DIALYSIS separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as HEMOFILTRATION or HEMODIAFILTRATION (if combined with HEMODIALYSIS).
D059005	Topoisomerase II Inhibitors	Compounds that inhibit the activity of DNA TOPOISOMERASE II. Included in this category are a variety of ANTINEOPLASTIC AGENTS which target the eukaryotic form of topoisomerase II and ANTIBACTERIAL AGENTS which target the prokaryotic form of topoisomerase II.	DNA Gyrase Inhibitor,DNA Topoisomerase II Inhibitor,Topoisomerase 2 Inhibitors,Topoisomerase II Inhibitor,DNA Gyrase Inhibitors,DNA Topoisomerase II Inhibitors,DNA Type 2 Topoisomerase Inhibitors,Gyrase Inhibitor, DNA,Gyrase Inhibitors, DNA,II Inhibitor, Topoisomerase,Inhibitor, DNA Gyrase,Inhibitor, Topoisomerase II,Inhibitors, DNA Gyrase,Inhibitors, Topoisomerase 2,Inhibitors, Topoisomerase II