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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Enantioselective pharmacokinetics of homochlorcyclizine: disposition of (+)- and (-)-homochlorcyclizine after intravenous and oral administration of racemic homochlorcyclizine to rats.

Concentrations of homochlorcyclizine enantiomers in blood, urine, and tissues of the liver, lung, kidney, brain, heart, spleen, intestine and stomach of rats after drug administration were determined by high-performance liquid chromatography on a chiral stationary phase. After intravenous administration (10 mg kg-1), homochlorcyclizine was rapidly distributed in many tissues, with the highest concentration in lung. No differences were found between enantiomers in blood concentrations. After oral administration (50 mg kg-1), the concentrations of the (+)-isomer in nearly all tissues were higher than those of the (-)-isomer. The AUC0-infinity values of the (+)- and (-)-isomers differed significantly. The absorption of racemic homochlorcyclizine from rat small intestine was not enantioselective. These results suggested that the different concentrations between enantiomers after oral administration were not caused by enantioselective absorption or distribution but rather by preferential first-pass metabolism of the (-)-isomer in the liver. The enantioselectivity of metabolism was also demonstrated by in-vitro experiments.[1]

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