title: Enantioselective Pharmacokinetics of α-Lipoic Acid in Rats.
abstract: α-Lipoic acid (LA) is widely used for nutritional supplements as a racemic mixture, even though the R enantiomer is biologically active. After oral administration of the racemic mixture (R-α-lipoic acid (RLA) and S-α-lipoic acid (SLA) mixed at the ratio of 50:50) to rats, RLA showed higher plasma concentration than SLA, and its area under the plasma concentration-time curve from time zero to the last (AUC) was significantly about 1.26 times higher than that of SLA. However, after intravenous administration of the racemic mixture, the pharmacokinetic profiles, initial concentration (C₀), AUC, and half-life (T1/2) of the enantiomers were not significantly different. After oral and intraduodenal administration of the racemic mixture to pyrolus-ligated rats, the AUCs of RLA were significantly about 1.24 and 1.32 times higher than that of SLA, respectively. In addition, after intraportal administration the AUC of RLA was significantly 1.16 times higher than that of SLA. In conclusion, the enantioselective pharmacokinetics of LA in rats arose from the fraction absorbed multiplied by gastrointestinal availability (FaFg) and hepatic availability (Fh), and not from the total clearance.
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan. j3b13702@ed.tus.ac.jp.
authors.forename: Ryota
authors.initials: R
authors.lastname: Uchida
authors.affiliation: CycloChem Bio Co., Ltd., KIBC654R 5-5-2 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. hinako.okamoto@cyclochem.com.|Graduate School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. hinako.okamoto@cyclochem.com.
authors.forename: Hinako
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Graduate School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. naoko.ikuta@people.kobe-u.ac.jp.
authors.forename: Naoko
authors.initials: N
authors.lastname: Ikuta
authors.affiliation: CycloChem Bio Co., Ltd., KIBC654R 5-5-2 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. keiji.terao@cyclochem.com.|Graduate School of Medicine, Kobe University, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan. keiji.terao@cyclochem.com.
authors.forename: Keiji
authors.initials: K
authors.lastname: Terao
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan. hirotas5@rs.noda.tus.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hirota
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D019587:Dietary Supplements / Q000032:analysis; D005753:Gastric Mucosa / Q000378:metabolism; D006207:Half-Life; D007408:Intestinal Absorption; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D008063:Thioctic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000975:Antioxidants; D008063:Thioctic Acid
keywords: clearance; enantioselective; gastrointestinal availability; hepatic availability; pharmacokinetics; rat; α-lipoic acid