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Pharmacokinetics of fexofenadine enantiomers in healthy subjects
Author(s) -
Miura Masatomo,
Uno Tsukasa,
Tateishi Tomonori,
Suzuki Toshio
Publication year - 2007
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.20370
Subject(s) - chemistry , fexofenadine , pharmacokinetics , enantiomer , pharmacology , stereochemistry , medicine
Fexofenadine, a substrate of P‐glycoprotein and an organic anion transporter polypeptide, is commonly used to assess P‐glycoprotein activity in vivo. The purpose of this study was to elucidate the pharmacokinetics of each fexofenadine enantiomer. After a single oral dose of racemic fexofenadine (60 mg), the plasma and urine concentrations of fexofenadine enantiomers were measured over the course of 24 h in six healthy subjects. The mean plasma concentration of R (+)‐fexofenadine was higher than that of S (−)‐fexofenadine. The area under the plasma concentration‐time curve (AUC 0–∞ ) and the maximum plasma concentration ( C max ) of R (+)‐fexofenadine were significantly greater than those of the S (−)‐enantiomer ( P = 0.0018 and 0.0028, respectively). The R / S ratios of AUC and C max of fexofenadine were 1.75 and 1.63, respectively. The oral clearance and renal clearance of S (−)‐fexofenadine were significantly greater than that of R (+)‐fexofenadine ( P = 0.0074 and 0.0036). On the other hand, the stereoselective metabolism of fexofenadine using recombinant CYP3A4 was investigated; however, fexofenadine enantiomers were not metabolized by CYP3A4. Fexofenadine is transported by both P‐glycoprotein and OATP and is not metabolized by intestinal CYP3A. Our findings suggest that the affinity of P‐glycoprotein for S (−)‐fexofenadine is greater than its affinity for the R (+)‐enantiomer. Thus, P‐glycoprotein is likely to have chiral discriminatory abilities. Chirality, 2007. © 2007 Wiley‐Liss, Inc.