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Enantioselective Pharmacokinetics of Carvedilol in Human Volunteers  

Phuong, Nuyen-Thi (College of Pharmacy, Chungnam National University)
Lee, Beam-Jin (College of Pharmacy, Kangwon National University)
Choi, Jung-Kap (College of Pharmacy, Chonnam National University)
Kang, Jong-Seong (College of Pharmacy, Chungnam National University)
Kwon, Kwang-il (College of Pharmacy, Chungnam National University)
Publication Information
Archives of Pharmacal Research / v.27, no.9, 2004 , pp. 973-977 More about this Journal
Abstract
Carvedilol is administered as a racemic mixture of the R(+)- and S(-)-enantiomers, although they exhibit different pharmacological effects. To investigate the stereoselective pharmacoki-netics, the enantiomeric separation of carvedilol in human plasma was undertaken using capil-lary electrophoresis (CE). Resolution of the enantiomers was achieved using 2-hydoxypropyl-$\beta$-cyclodextrin as the chiral selector. Phosphate buffer (50 mM, pH 4.0) containing 10 mM of 2-hydoxypropropyl-$\beta$-cyclodextrin was used as electrolytic buffer. Achiral separation was carried out with the same electrolytic buffer without chiral selector. Following a single oral administra-tion of 25-mg carvedilol to 11 healthy, male volunteers, stereoselective pharmacokinetic analy-sis was undertaken. The maximum plasma concentrations ( $C_{max}$) were 48.9 and 21.6 ng/mL for (R)-carvedilol and (S)-carvedilol, respectively, determined by the chiral method. The profiles of the plasma concentration of (RS)-carvedilol showed $C_{max}$ of 71.5, 72.2, and 73.5 ng/mL, as determined by the CE, HPLC/FD methods and calculations from the data of the chiral method, respectively.y.y.
Keywords
Carvedilol; Pharmacokinetics; Stereospecificity; Human plasma; Capillary electro- phoresis; 2-Hydoxypropyl-$\beta$-cyclodextrin;
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