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Bidirectional Chiral Inversion of Trantinterol Enantiomers After Separate Doses to Rats
Author(s) -
Qin Feng,
Wang Xintao,
Jing Lijuan,
Pan Li,
Cheng Maosheng,
Sun Guoxiang,
Li Famei
Publication year - 2013
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.22236
Subject(s) - chemistry , enantiomer , inversion (geology) , chirality (physics) , stereochemistry , combinatorial chemistry , chiral perturbation theory , nuclear physics , biology , paleontology , pion , nambu–jona lasinio model , physics , structural basin
The chiral inversion and pharmacokinetics of two enantiomers of trantinterol, a new β 2 agonist, were studied in rats dosed (+)‐ or (−)‐trantinterol separately. Plasma concentrations of (+)‐ and (−)‐trantinterol were measured by chiral stationary phase liquid chromatography tandem mass spectroscopy (LC‐MS/MS). The apparent inversion ratio was calculated as the ratio of AUC 0‐t of (−)‐trantinterol or (+)‐trantinterol inverted from their antipodes to the sum of the AUC 0‐t of (−)‐ and (+)‐trantinterol. Following single intravenous administration, both given enantiomers declined in similar plasma concentrations, suggesting that the two enantiomers have approximately the same disposition kinetics by the route of intravenous administration. However, after single oral administration, plasma concentrations of uninverted (−)‐trantinterol at many timepoints were significantly higher than those of uninverted (+)‐trantinterol, suggesting that the two enantiomers undergo apparently different absorption or metabolism after oral administration. Significant bidirectional chiral inversion occurred after intravenous and oral administration of (+)‐ or (−)‐trantinterol. After dosing with optically pure enantiomer, the concentration of the administered enantiomer predominated in vivo. The AUC 0‐36 of (+)‐trantinterol after intravenous and oral dosing of (−)‐trantinterol were 16.6 ± 5.2 and 33.3 ± 16%, respectively of those of total [(+) + (−)] trantinterol. The AUC 0‐36 of (−)‐trantinterol after intravenous and oral dosing of (+)‐trantinterol were 19.6 ± 8.8 and 37.9 ± 4.5%, respectively, of those of total [(−) + (+)] trantinterol. After intravenous administration of (+)‐ and (−)‐trantinterol the chiral inversion ratios of the two enantiomers were not significantly different and similar results were found for oral administration. The extent of chiral inversion after intravenous administration was apparently lower, indicating that the bidirectional chiral inversion was not only systemic but also presystemic. Chirality 25:934–938, 2013. © 2013 Wiley Periodicals, Inc.