Drug protein binding in chronic renal failure : evaluation of nine drugs

R. Vanholder, N. Landschoot, van, R. DeSmet, A.C. Schoots, S.M.G. Ringoir

Research output: Contribution to journalArticleAcademicpeer-review

138 Citations (Scopus)

Abstract

Drug protein binding in chronic renal failure: Evaluation of nine drugs. 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 <0.001), and a less pronounced but still significant positive correlation was found for clonidine (r = 0.46, P <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. Furthermore, hippuric acid appears to play an important role in the defect of the protein binding of theophylline and phenytoin.
Original languageEnglish
Pages (from-to)996-1004
Number of pages9
JournalKidney International
Volume33
Issue number5
DOIs
Publication statusPublished - 1988

Fingerprint

Dive into the research topics of 'Drug protein binding in chronic renal failure : evaluation of nine drugs'. Together they form a unique fingerprint.

Cite this