Document Detail


Enantioselective local disposition of semotiadil (R-enantiomer) and levosemotiadil (S-enantiomer) in perfused rat liver.
MedLine Citation:
PMID:  9172944     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The enantioselective local disposition of semotiadil (R-enantiomer) and levosemotiadil (S-enantiomer) in rat liver was investigated in the single-pass perfusion system containing 1% bovine serum albumin (BSA). After an instantaneous injection of semotiadil, levosemotiadil, or Evans Blue (a marker of BSA), each outflow time profile from the liver was analyzed by a two-compartment dispersion model. The recovery ratio, FH (1.88 +/- 0.28%), of semotiadil was significantly smaller than that (8.99 +/- 1.40%) of levosemotiadil. The mean transit time, fH (0.146 +/- 0.014 min) of semotiadil was significantly smaller than that (0.191 +/- 0.012 min) of levosemotiadil. The biliary excretion kinetics of these enantiomers was also evaluated by moment analysis. The parent compound (semotiadil or levosemotiadil) was not detected in bile, but four metabolites generated from each parent enantiomer were found in the bile. A portion (16.5 +/- 1.2%) of the drug eliminated by the liver was recovered as R-metabolites in the bile within 1 hr after an injection of semotiadil, whereas 11.2 +/- 1.6% was recovered as S-metabolites in the bile within 1 hr after an injection of levosemotiadil. This excreted percentage into the bile was significantly different between R- and S-metabolites. The mean biliary excretion time MRTe (19.1 +/- 2.2 min) of total R-metabolites was significantly larger than that (14.8 +/- 1.1 min) of total S-metabolites. In conclusion, stereo-selectivity was suggested both at the hepatic elimination of the parent compound and at the biliary excretion of the metabolites.
Authors:
K Ueda; K Yamaoka; M E Rodriguez; A Shibukawa; T Nakagawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  25     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:  1997 Mar 
Date Detail:
Created Date:  1997-06-05     Completed Date:  1997-06-05     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  281-6     Citation Subset:  IM    
Affiliation:
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium Channel Blockers / pharmacokinetics*
Evans Blue
Liver / metabolism*
Male
Perfusion
Rats
Rats, Wistar
Serum Albumin, Bovine / pharmacokinetics
Stereoisomerism
Thiazoles / pharmacokinetics*
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Serum Albumin, Bovine; 0/Thiazoles; 116476-14-3/sesamodil; 314-13-6/Evans Blue

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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