Pharmacokinetic evidence for saturable renal tubular reabsorption of riboflavin

✍ Scribed by William J. Jusko; Gerhard Levy

• Publisher: John Wiley and Sons
• Year: 1970
• Tongue: English
• Weight: 844 KB
• Volume: 59
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600590608

✦ Synopsis

a possible "active" process, could be postulated, it appears more reasonable to be critical of the assumption of rate-determining drug diffusion into the biophase.

An alternate explanation may be that drug action, as manifested by the degree of inhibition of generation rate, increases the sensitivity of the organism to further drug action until the steady-state generation rate is achieved. This "feedback" phenomenon is explainable on the premise that the rapidly equilibrated drug concentration in the biophase is competitive for receptor sites with a metabolic intermediate produced by the growing organism.

An analogy can be drawn to thesulfonamide-p-aminobenzoic acid competition. The initial fraction of receptor sites that is drugreceptor complex is reflected by an initial decrease in generation rate. This results in a diminution of the production ofa vital metabolic intermediate. Subsequent depletion of excess stores of this intermediate in the normal metabolic or generation processes of the organism results in less amounts to compete with drug concentrations in the biophase, greater fractions of drug-receptor complex, and, consequently, further slowing of generation rates. On dilution of the drug with fresh medium, the drug in the organism's biophase rapidly reequilibrates with the consequence of less drug-bound receptor sites. A new steady-state production of metabolic intermediate may occur. This results in the observed reasonably rapid increase in microbial generation to new steady-state conditions (Fig. ). A kinetically equivalent phenomenon is that the feedback is mediated by decreasing the number of available receptor sites concomitant with decreasing growth rates.