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In this study, changes of protein binding of nine drugs were evaluated. In addition, theophylline and phenytoin, the two drugs with the most substantial and progressive decrease in protein binding, were further studied by high performance liquid chromatography (HPLC)-fractions of ultrafiltrate of normal and uremic serum, in an attempt to identify substances causing drug protein binding inhibition. There was a marked decline of the protein binding of theophylline, phenytoin and methotrexate (dialyzed patients vs. normals: -20.1, -16.0 and -15.1%, respectively). There was a rise in the protein binding of propranolol, cimetidine and clonidine. The changes observed for diazepam, prazosin and imipramine were less marked. For phenytoin, theophylline, methotrexate and diazepam, protein binding was inversely correlated to the serum creatinine (r = 0.87, 0.80, 0.79 and 0.67, P less than 0.001), and a less pronounced but still significant positive correlation was found for clonidine (r = 0.46, P less than 0.01). Ultrafiltrate, obtained during a hemofiltration session, inhibited protein binding of theophylline and phenytoin in a dose dependent way. After separation of this ultrafiltrate by HPLC, it appeared that for both theophylline and phenytoin at least a part of this inhibitory activity corresponded to the elution zone of hippuric acid. For theophylline two other inhibitory zones were further recognized: one corresponding to the elution zone of NaCl and one in which the responsible substance remained unidentified. Hippuric acid in solution inhibited protein binding of theophylline and phenytoin in a dose dependent way. In conclusion, protein binding of several drugs currently used in renal failure is affected in parallel with renal function, which might affect the therapeutic effectiveness of the drugs.(ABSTRACT TRUNCATED AT 250 WORDS)
R Vanholder, and
N Van Landschoot, and
R De Smet, and
A Schoots, and
S Ringoir
January 1986,
Nephrologie,
R Vanholder, and
N Van Landschoot, and
R De Smet, and
A Schoots, and
S Ringoir
January 1987,
Therapie,
R Vanholder, and
N Van Landschoot, and
R De Smet, and
A Schoots, and
S Ringoir
September 1992,
Hospital formulary,
R Vanholder, and
N Van Landschoot, and
R De Smet, and
A Schoots, and
S Ringoir
March 1996,
The Japanese journal of antibiotics,
R Vanholder, and
N Van Landschoot, and
R De Smet, and
A Schoots, and
S Ringoir
September 1987,
International journal of clinical pharmacology, therapy, and toxicology,
R Vanholder, and
N Van Landschoot, and
R De Smet, and
A Schoots, and
S Ringoir
January 1973,
Acta pharmacologica et toxicologica,
R Vanholder, and
N Van Landschoot, and
R De Smet, and
A Schoots, and
S Ringoir
April 1993,
The Japanese journal of antibiotics,
R Vanholder, and
N Van Landschoot, and
R De Smet, and
A Schoots, and
S Ringoir
April 2003,
Current drug metabolism,
R Vanholder, and
N Van Landschoot, and
R De Smet, and
A Schoots, and
S Ringoir
July 1994,
International journal of clinical pharmacology and therapeutics,
R Vanholder, and
N Van Landschoot, and
R De Smet, and
A Schoots, and
S Ringoir
January 1993,
European journal of clinical pharmacology,
