Accumulation of furancarboxylic acids in uremic serum as inhibitors of drug binding.
3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, 3-carboxy-4-methyl-5-pentyl-2-furanpropionic acid, 3-carboxy-4-methyl-5-ethyl-2-furanpropionic acid and 3-carboxy-5-propyl-2-furanpropionic acid were detected in uremic serum using gas chromatography-mass spectrometry. Mass chromatography revealed that the serum concentrations of the furancarboxylic acids especially 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, were increased in the chronic hemodialysis patients and that the acids could not be removed by conventional hemodialysis due to their strong binding to plasma protein. 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid was also quantitated in uremic serum by high-performance liquid chromatography. Serum level of the acid in uremic patients showed significant but weak correlation with serum level of urea and duration on hemodialysis. Equilibrium dialysis demonstrated that 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid and 3-carboxy-4-methyl-5-pentyl-2-furanpropionic acid inhibited the bindingof salicylate and 5,5-diphenylhydantoin to albumin. In conclusion, the furancarboxylic acids especially 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid were accumulated in uremic serum as inhibitors of drug binding.
Niwa
T
T
Department of Internal Medicine, Nagoya University Branch Hospital, Higashi-ku, Japan.
Takeda
N
N
Maeda
K
K
Shibata
M
M
Tatematsu
A
A
D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005663:Furans / Q000097:blood*; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011422:Propionates / Q000097:blood*; D006435:Renal Dialysis; D012459:Salicylates / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism; D014511:Uremia / Q000097:blood*
D002352:Carrier Proteins; D005663:Furans; D011422:Propionates; D012459:Salicylates; D012709:Serum Albumin; C056278:3-carboxy-4-methyl-5-ethyl-2-furanpropionic acid; C056280:3-carboxy-4-methyl-5-pentyl-2-furanpropionic acid; C056281:3-carboxy-5-propyl-2-furanpropionic acid; C041693:3-carboxy-4-methyl-5-propyl-2-furanpropionic acid