Renal transport mechanisms for xenobiotics: chemicals and drugs

1993 ◽  
Vol 71 (10) ◽  
Author(s):  
K.J. Ullrich ◽  
G. Rumrich
Keyword(s):  
Renal Transport ◽  
Transport Mechanisms

scholarly journals Effects of Organic Anion, Organic Cation, and Dipeptide Transport Inhibitors on Cefdinir in the Isolated Perfused Rat Kidney

2003 ◽  
Vol 47 (2) ◽  
pp. 689-696 ◽  
Author(s):  
Christopher S. Lepsy ◽  
Robert J. Guttendorf ◽  
Alan R. Kugler ◽  
David E. Smith
Keyword(s):  
Organic Cation ◽  
Rat Kidney ◽  
Organic Anion ◽  
Renal Elimination ◽  
Renal Transport ◽  
Transport Mechanisms ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney ◽  
Transport Inhibitors ◽  
Dipeptide Transport

ABSTRACT Cefdinir (Omnicef; Abbott Laboratories) is a cephalosporin antibiotic primarily eliminated by the kidney. Nonlinear renal elimination of cefdinir has been previously reported. Cefdinir renal transport mechanisms were studied in the erythrocyte-free isolated perfused rat kidney. Studies were performed with drug-free perfusate and perfusate containing cefdinir alone to establish the baseline physiology and investigate cefdinir renal elimination characteristics. To investigate cefdinir renal transport mechanisms, inhibition studies were conducted by coperfusing cefdinir with inhibitors of the renal organic anion (probenecid), organic cation (tetraethylammonium), or dipeptide (glycylsarcosine) transport system. Cefdinir concentrations in biological samples were determined using reversed-phase high-performance liquid chromatography. Differences between treatments and controls were evaluated using analysis of variance and Dunnett's test. The excretion ratio (ER; the renal clearance corrected for the fraction unbound and glomerular filtration rate) for cefdinir was 5.94, a value indicating net renal tubular secretion. Anionic, cationic, and dipeptide transport inhibitors all significantly affected the cefdinir ER. With probenecid, the ER was reduced to 0.59, clearly demonstrating a significant reabsorptive component to cefdinir renal disposition. This finding was confirmed by glycylsarcosine studies, in which the ER was elevated to 7.95, indicating that reabsorption was mediated, at least in part, by the dipeptide transporter system. The effects of the organic cation tetraethylammonium, in which the ER was elevated to 7.53, were likely secondary in nature. The anionic secretory pathway was found to be the predominant mechanism for cefdinir renal excretion.

Drug Interactions Involving Renal Transport Mechanisms: An Overview

DICP ◽  
1989 ◽  
Vol 23 (2) ◽  
pp. 116-122 ◽  
Author(s):  
Teddy Kosoglou ◽  
Peter H. Vlasses
Keyword(s):  
Organic Acids ◽  
Drug Interactions ◽  
Clinical Studies ◽  
Renal Transport ◽  
Transport Mechanisms ◽  
Cellular Mechanisms ◽  
Cationic Drugs ◽  
Tubular Transport ◽  
Underlying Mechanisms ◽  
Complex Drug

The renal anatomy, physiology, and cellular mechanisms involved in tubular transport of organic acids (anions) and bases (cations) are reviewed. Drugs that are renally secreted are prone to significant and complex drug-drug interactions, and knowledge of the underlying mechanisms is important. Several clinical studies involving commonly used cationic drugs (e.g., cimetidine, trimethoprim, and procainamide) are cited as examples of drug interactions involving renal transport mechanisms.

Do recommended textbooks contain adequate information about bile salt transporters for medical students?

2004 ◽  
Vol 28 (2) ◽  
pp. 36-43 ◽  
Author(s):  
Samy A. Azer
Keyword(s):  
Bile Salt ◽  
Bile Salts ◽  
Renal Transport ◽  
Transport Mechanisms ◽  
Research Knowledge ◽  
Bile Formation ◽  
Amount Of Information ◽  
The Past ◽  
Adequate Information ◽  
Bile Salt Transporters

Several studies have recently highlighted a number of limitations in medical textbooks. The aims of this study were to 1) to assess whether available medical textbooks provided students with adequate information about bile salt transporters, 2) compare the level of detail and the amount of information provided in current textbooks on hepatic transport mechanisms with those available in the literature, and 3) compare the amount of information provided in medical textbooks on hepatocyte transport mechanisms with those involving other transporters e.g., those found in the nephron. Seventy medical textbooks from disciplines including physiology, pathology, cell biology, medicine, pediatrics, pharmacology, pathophysiology, and histology published during the past six years were examined. The literature on bile salt transport has been searched mainly from the Internet (MEDLINE and PubMed). Most textbooks failed to provide any information on transporters found in the basolateral and canalicular membranes of hepatocytes. There are also deficiencies in information on bile salt transporters in the terminal ileum. However, up to the end of 2002, 3,610 articles and reviews had been published on hepatobiliary and enterocyte transport of bile salts. During the same period (from 1965), 10,757 articles had been published on renal transport. Thus the contents of textbooks may reflect the overall volume of research knowledge on renal transport. However, despite our current understanding of hepatic and intestinal transport of bile salts and extensive research, particularly over the past 12 years, there are major deficiencies in textbooks in this area. These findings indicate that there is an imbalance in the contents of current textbooks and a lack of information about hepatobiliary physiology, bile salt transporters, bile formation, and mechanisms underlying cholestasis and drug-induced injury. Authors, editors, and publishers of medical textbooks should consider the need to update the information provided on bile salt transporters.

Renal Transport Mechanisms

2013 ◽  
pp. 45-71 ◽  
Author(s):  
Bruce M. Koeppen ◽  
Bruce A. Stanton
Keyword(s):  
Renal Transport ◽  
Transport Mechanisms

Renal transport sites for K, H and NH3. Effect of impermeant anions on their transport

1960 ◽  
Vol 198 (2) ◽  
pp. 244-254 ◽  
Author(s):  
Lawrence P. Sullivan ◽  
Walter S. Wilde ◽  
Richard L. Malvin
Keyword(s):  
Negative Charge ◽  
Distal Tubule ◽  
Sodium Reabsorption ◽  
Renal Transport ◽  
Transport Mechanisms ◽  
Collecting Ducts ◽  
Tubular Lumen ◽  
Potassium Hydrogen ◽  
A Site ◽  
Stop Flow

The stop flow technique was used to locate the sites of the renal transport mechanisms for potassium, hydrogen and ammonium. Data were obtained which indicate that these cations are secreted in a very distal area of the nephron, presumably in the collecting ducts. Potassium reabsorption also occurs in a distal area immediately proximal to the secretory site. Infusions of thiosulfate, ferrocyanide and phosphate alter the stop flow concentration patterns so that secretion of the cations appears to take place throughout the distal tubule and to be coextensive with distal sodium reabsorption. No clear indication of potassium reabsorption is evident under these circumstances. It is suggested that these anions, because of the impermeability of the distal tubule to them and because of their negative charge, attract hydrogen and potassium into the tubular lumen as sodium is reabsorbed. In effect, an abnormal exchange mechanism is created at a site proximal to that where active secretion of hydrogen and potassium occurs.

Physical Properties of Isolated Perfused Renal Tubular Basement Membranes

1971 ◽  
Vol 29 ◽  
pp. 390-391
Author(s):  
Jared Grantham ◽  
Larry Welling
Keyword(s):  
Basement Membrane ◽  
Basement Membranes ◽  
Transport Mechanisms ◽  
Permeability Characteristics ◽  
Peritubular Capillaries ◽  
Strategic Location ◽  
Tubular Lumen ◽  
Glomerular Filtrate ◽  
Urine Formation ◽  
Renal Tubular

In the course of urine formation in mammalian kidneys over 90% of the glomerular filtrate moves from the tubular lumen into the peritubular capillaries by both active and passive transport mechanisms. In all of the morphologically distinct segments of the renal tubule, e.g. proximal tubule, loop of Henle and distal nephron, the tubular absorbate passes through a basement membrane which rests against the basilar surface of the epithelial cells. The basement membrane is in a strategic location to affect the geometry of the tubules and to influence the movement of tubular absorbate into the renal interstitium. In the present studies we have determined directly some of the mechanical and permeability characteristics of tubular basement membranes.

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