title: Investigation of Enantioselective Membrane Permeability of α-Lipoic Acid in Caco-2 and MDCKII Cell.
abstract: α-Lipoic acid (LA) contains a chiral carbon and exists as two enantiomers (R-α-lipoic acid (RLA) and S-α-lipoic acid (SLA)). We previously demonstrated that oral bioavailability of RLA is better than that of SLA. This difference arose from the fraction absorbed multiplied by gastrointestinal availability (F(a) × F(g)) and hepatic availability (F(h)) in the absorption phase. However, it remains unclear whether F(a) and/or F(g) are involved in enantioselectivity. In this study, Caco-2 cells and Madin-Darby canine kidney strain II cells were used to assess the enantioselectivity of membrane permeability. LA was actively transported from the apical side to basal side, regardless of the differences in its steric structure. Permeability rates were proportionally increased in the range of 10-250 µg LA/mL, and the permeability coefficient did not differ significantly between enantiomers. Hence, we conclude that enantioselective pharmacokinetics arose from the metabolism (F(h) or F(g) × F(h)), and definitely not from the membrane permeation (F(a)) in the absorption phase.
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: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability / Q000187:drug effects*; D004285:Dogs; D006801:Humans; D007408:Intestinal Absorption; D061985:Madin Darby Canine Kidney Cells; D013237:Stereoisomerism; D008063:Thioctic Acid / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*
chemical_list: D008063:Thioctic Acid
keywords: Caco-2; MDCKII; enantioselective; gastrointestinal availability; hepatic availability; membrane permeability; pharmacokinetics; α-lipoic acid
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