Biomaterial Database

Effect of cilastatin on renal handling of vancomycin in rats. 1998

M Kusama, and K Yamamoto, and H Yamada, and H Kotaki, and H Sato, and T Iga

Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.

To provide insights into the possibility of reducing the nephrotoxicity of vancomycin (VCM) by cilastatin, the effect of cilastatin on the renal handling of VCM, as well as on glomerular filtration rate (GFR) and plasma protein binding of VCM, were studied using rats. After a bolus intravenous (iv) dose of VCM (100 mg/kg), concomitant cilastatin administration (100 mg/kg, iv) resulted in a significant increase in the total VCM clearance and significant decrease in the kidney uptake clearance of VCM, defined as kidney VCM concentration vs AUC ratio. Moreover, after a 3-h continuous iv infusion of VCM (18 or 90 mg/h/kg), significant decrease in the kidney uptake clearance of VCM was observed with concomitant cilastatin iv infusion (300 mg/h/kg). On the other hand, GFR and VCM plasma protein binding did not show any significant change with cilastatin. From the observation that cilastatin decreased the kidney uptake clearance of VCM and enhanced its urinary excretion, it was suggested that cilastatin inhibited the reabsorption of VCM in the renal proximal tubular cells. Thus, it may be possible that cilastatin alleviates the nephrotoxicity of VCM due to reduced accumulation and accelerated renal excretion of VCM.

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D008297	Male		Males
D008657	Metabolic Clearance Rate	Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site.	Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D011480	Protease Inhibitors	Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).	Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
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
D006207	Half-Life	The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.	Halflife,Half Life,Half-Lifes,Halflifes
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
D000900	Anti-Bacterial Agents	Substances that inhibit the growth or reproduction of BACTERIA.	Anti-Bacterial Agent,Anti-Bacterial Compound,Anti-Mycobacterial Agent,Antibacterial Agent,Antibiotics,Antimycobacterial Agent,Bacteriocidal Agent,Bacteriocide,Anti-Bacterial Compounds,Anti-Mycobacterial Agents,Antibacterial Agents,Antibiotic,Antimycobacterial Agents,Bacteriocidal Agents,Bacteriocides,Agent, Anti-Bacterial,Agent, Anti-Mycobacterial,Agent, Antibacterial,Agent, Antimycobacterial,Agent, Bacteriocidal,Agents, Anti-Bacterial,Agents, Anti-Mycobacterial,Agents, Antibacterial,Agents, Antimycobacterial,Agents, Bacteriocidal,Anti Bacterial Agent,Anti Bacterial Agents,Anti Bacterial Compound,Anti Bacterial Compounds,Anti Mycobacterial Agent,Anti Mycobacterial Agents,Compound, Anti-Bacterial,Compounds, Anti-Bacterial
D001682	Biological Availability	The extent to which the active ingredient of a drug dosage form becomes available at the site of drug action or in a biological medium believed to reflect accessibility to a site of action.	Availability Equivalency,Bioavailability,Physiologic Availability,Availability, Biologic,Availability, Biological,Availability, Physiologic,Biologic Availability,Availabilities, Biologic,Availabilities, Biological,Availabilities, Physiologic,Availability Equivalencies,Bioavailabilities,Biologic Availabilities,Biological Availabilities,Equivalencies, Availability,Equivalency, Availability,Physiologic Availabilities
D014640	Vancomycin	Antibacterial obtained from Streptomyces orientalis. It is a glycopeptide related to RISTOCETIN that inhibits bacterial cell wall assembly and is toxic to kidneys and the inner ear.	AB-Vancomycin,Diatracin,VANCO-cell,Vanco Azupharma,Vanco-saar,Vancocin,Vancocin HCl,Vancocine,Vancomicina Abbott,Vancomicina Chiesi,Vancomicina Combino Phar,Vancomicina Norman,Vancomycin Hexal,Vancomycin Hydrochloride,Vancomycin Lilly,Vancomycin Phosphate (1:2),Vancomycin Phosphate (1:2), Decahydrate,Vancomycin Sulfate,Vancomycin-ratiopharm,Vancomycine Dakota,Hydrochloride, Vancomycin,Sulfate, Vancomycin