Bidirectional Chiral Inversion of Trantinterol Enantiomers After Separate Doses to Rats. Issue 12 (30th September 2013)

• Record Type: Journal Article
• Authors: Qin, Feng; Wang, Xintao; Jing, Lijuan; Pan, Li; Cheng, Maosheng; Sun, Guoxiang; Li, Famei
• Is Part Of: Chirality. Volume 25:Issue 12(2013:Dec.)
• Page Start: 934
• Page End: 938
• Publication Date: 2013-09-30
• Subjects: Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.22236
• Languages: English
• ISSNs: 0899-0042

Abstract

<abstract abstract-type="main"> <title>ABSTRACT</title> <p>The chiral <named-content id="d580e443" content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">inversion</named-content> and pharmacokinetics of two enantiomers of trantinterol, a new β<sub>2</sub> agonist, were studied in rats dosed (+)‐ or (−)‐trantinterol separately. Plasma concentrations of (+)‐ and (−)‐trantinterol were measured by chiral stationary phase <named-content id="d580e449" content-type="chemicalTechnology" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">liquid chromatography</named-content> tandem mass spectroscopy (LC‐MS/MS). The apparent <named-content id="d580e452" content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">inversion</named-content> ratio was calculated as the ratio of AUC<sub>0‐t</sub> of (−)‐trantinterol or (+)‐trantinterol inverted from their antipodes to the sum of the AUC<sub>0‐t</sub> 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 <named-content id="d580e462" content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">inversion</named-content> 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<sub>0‐36</sub> 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<sub>0‐36</sub> 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 <named-content id="d580e471" content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">inversion</named-content> ratios of the two enantiomers were not significantly different and similar results were found for oral administration. The extent of chiral <named-content id="d580e474" content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">inversion</named-content> after intravenous administration was apparently lower, indicating that the bidirectional chiral <named-content id="d580e478" content-type="reactionType" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink">inversion</named-content> was not only systemic but also presystemic. <italic>Chirality 25:934–938, 2013.</italic>© 2013 Wiley Periodicals, Inc.</p> </abstract>