Influence of Uremic Toxins and Nonesterified Fatty Acids on Drug and Thyroid Hormone Binding in Serum

Abstract

The findings of Takamura et al. (1) suggest that the furan fatty acid 3-carboxy-4-methyl-5-propyl-2-furan propionate (CMPF) is the major uremic toxin that inhibits albumin binding of the drug furosemide in chronic renal failure. These authors also invoke a potentially important cascade mechanism that can increase the unbound concentration of furosemide as a result of increased occupancy of drug binding sites on albumin by CMPF or oleate. To place these important observations in context, we wish to comment on the following: (a) the relevance of cascade effects in influencing the unbound concentrations of numerous other drugs such as aspirin and nonsteroidal antiinflammatory agents; (b) the importance of a similar cascade effect as a mechanism that can increase free thyroid hormone concentrations; and (c) the potential to overestimate the …