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Stereoselective protein binding of alprenolol in the renal diseased state
Author(s) -
Imamura Hitoshi,
Komori Takafumi,
Ismail Ahmed,
Suenaga Ayaka,
Otagiri Masaki
Publication year - 2002
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.10097
Subject(s) - alprenolol , chemistry , stereoselectivity , ultrafiltration (renal) , endogeny , pharmacology , stereochemistry , biochemistry , receptor , medicine , catalysis
The investigation was undertaken to study the stereoselective protein binding of alprenolol in renal disease patient sera, compared to that in the sera of healthy volunteers. The in vitro stereoselective protein binding of β‐blockers was determined in undiluted serum and in isolated α 1 ‐acid glycoprotein (AGP) solutions by ultrafiltration. The stereoselctive serum protein binding of alprenolol, a β‐adrenergic blocking agent, in healthy volunteers was significantly altered in renal disease patients. We investigated the effects of AGP concentration and endogenous substances, including uremic toxins, on the stereoselective protein binding of alprenolol in renal disease patients. A good correlation between the unbound (R)/(S) ratio (F R /F S ratio), an apparent index of stereoselectivity in alprenolol serum binding and AGP concentration in serum, was found. However, stereoselective protein binding was not influenced by endogenous substances. This result can be explained by the difference in binding affinities of (R) and (S)‐isomers of alprenolol to AGP. We conclude that the stereoselective protein binding of alprenolol in healthy volunteers and renal disease patients varies as a result of changes in AGP concentration. Accordingly, these findings might be useful in alprenolol therapy in renal disease patients. Chirality 14:599–603, 2002. © 2002 Wiley‐Liss, Inc.