title: Enantioselective pharmacokinetics of doxazosin and pharmacokinetic interaction between the isomers in rats.
abstract: In this study, the stereoselective pharmacokinetics of doxazosin enantiomers and their pharmacokinetic interaction were studied in rats. Enantiomer concentrations in plasma were measured using chiral high-pressure liquid chromatography (HPLC) with fluorescence detection after oral or intravenous administration of (-)-(R)-doxazosin 3.0 mg/kg, (+)-(S)-doxazosin 3.0 mg/kg, and rac-doxazosin 6.0 mg/kg. AUC values of (+)-(S)-doxazosin were always larger than those of (-)-(R)-doxazosin, regardless of oral or intravenous administration. The maximum plasma concentration (Cmax ) value of (-)-(R)-doxazosin after oral administration was significantly higher when given alone (110.5 ± 46.4 ng/mL) versus in racemate (53.2 ± 19.7 ng/mL), whereas the Cmax value of (+)-(S)-doxazosin did not change significantly. The area under the curve (AUC) and Cmax values for (+)-(S)-doxazosin after intravenous administration were significantly lower, and its Cl value significantly higher, when given alone versus in racemate. We speculate that (-)-(R)-doxazosin increases (+)-(S)-doxazosin exposure probably by inhibiting the elimination of (+)-(S)-doxazosin, and the enantiomers may be competitively absorbed from the gastrointestinal tract. In conclusion, doxazosin pharmacokinetics are substantially stereospecific and enantiomer-enantiomer interaction occurs after rac-administration.
authors.affiliation: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Dezhi
authors.initials: D
authors.lastname: Kong
authors.affiliation: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Du
authors.affiliation: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Yaqin
authors.initials: Y
authors.lastname: Zhen
authors.affiliation: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Tonghui
authors.initials: T
authors.lastname: Li
authors.affiliation: Institute of Chinese Integrative Medicine, Hebei Medical University, Shijiazhuang, China.
authors.forename: Leiming
authors.initials: L
authors.lastname: Ren
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D017292:Doxazosin / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013237:Stereoisomerism
chemical_list: D017292:Doxazosin
keywords: doxazosin; enantiomer-enantiomer interaction; enantioselective; pharmacokinetics; rat