Premium
Intestinal absorption and metabolism of chlorpheniramine enantiomers in rat
Author(s) -
Hiep Bui Tung,
Fernandez Christine,
Tod Michel,
Banide Hélène,
Thuillier Alain,
Lacour Bernard,
Farinotti Robert,
Gimenez François
Publication year - 2001
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.1021
Subject(s) - stereoselectivity , chemistry , enantiomer , pharmacokinetics , in vivo , absorption (acoustics) , oral administration , metabolism , pharmacology , stereochemistry , metabolite , biochemistry , biology , physics , microbiology and biotechnology , acoustics , catalysis
Chlorpheniramine (CPAM) is a chiral antihistaminic drug commercialized as a racemic mixture. The intestinal absorption and metabolism of CPAM have been investigated in rat using in vivo (oral and IV administration), in situ (intestinal loop model), and in vitro (everted sac model) experiments. Oral and IV administrations of 20 mg/kg of the racemic mixture show that the pharmacokinetics of CPAM are stereoselective, with higher AUCs for the (+)‐S‐enantiomer compared to its antipode. The monodesmethyl metabolite (DCPM) was quantifiable in blood and its pharmacokinetics are stereoselective after oral but not after IV administration. Experiments using intestinal loops and everted sacs showed that the absorption is not stereoselective and that in vivo stereoselective formation of DCPM is presumably due to stereoselective hepatic metabolism. Moreover, the in vitro and in situ absorption of CPAM are not modified by modulators of P‐glycoprotein and cytochromes P450 (cyclosporin A, ketoconazole). Chirality 13:207–213, 2001. © 2001 Wiley‐Liss, Inc.