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Stereoselective biliary elimination of disopyramide and mono‐ N ‐desisopropyldisopyramide in humans
Author(s) -
Corre Pascal Le,
Malledant Yannick,
Chevanne Francois,
Sado Pierre,
Verge Roger Le
Publication year - 1992
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.530040203
Subject(s) - chemistry , stereoselectivity , enantiomer , pharmacokinetics , disopyramide , stereochemistry , pharmacology , medicine , biochemistry , catalysis
The results of a previous pharmacokinetic study of disopyramide (DP) enantiomers in humans suggested that DP and/or mono‐ N ‐desisopropyldisopyramide (MND) may show stereoselective extrarenal elimination. Thus, the present study investigates the biliary elimination of DP and MND enantiomers in three patients who had undergone cholecystectomy for cholelithiasis. DP and MND enantiomers displayed biliary elimination. In both subjects, this elimination pathway showed the same characteristics: (1) biliary elimination of DP and MND was stereoselective, (2) the stereoselectivity was opposite to that observed for the metabolic and renal elimination pathways, i.e., the elimination of the (−)‐(R)‐enantiomer was higher than that of the (+)‐(S)‐enantiomer, and (3) biliary elimination of MND was higher than that of DP, for both enantiomers. Estimates of the relative contribution of the biliary clearance in the total clearance of DP and MND indicated that this elimination pathway was secondary, especially for DP. The biliary clearance (expressed as % of total clearance) was 1.9 to 4.0% for (−)‐(R)‐DP, 1.2 to 1.7% for (+)‐(S)‐DP, 7.8 to 22.9% for (−)‐(R)‐MND, and 5.2 to 10.5% for (+)‐(S)‐MND.