title: Effect of γ-Cyclodextrin Inclusion Complex on the Absorption of R-α-Lipoic Acid in Rats.
abstract: R-α-lipoic acid (RLA) is an endogenous organic acid, and works as a cofactor for mitochondrial enzymes and as a kind of antioxidant. Inclusion complexes of RLA with α-, β- or γ-cyclodextrins (CD) were prepared and orally administered as a suspension to rats. Among them, RLA/γ-CD showed the highest plasma exposure, and its area under the plasma concentration-time curve (AUC) of RLA was 2.2 times higher than that after oral administration of non-inclusion RLA. On the other hand, the AUC after oral administration of non-inclusion RLA and RLA/γ-CD to pylorus-ligated rats did not differ. However, the AUC after intraduodenal administration of RLA/γ-CD was 5.1 times higher than that of non-inclusion RLA, and was almost comparable to the AUC after intraduodenal administration of RLA-Na solution. Furthermore, the AUC after intraduodenal administration of RLA/γ-CD was not affected by biliary ligation or co-administration of an amylase inhibitor. These findings demonstrated that RLA was absorbed from the small intestine effectively when orally administered as a γ-CD inclusion complex, which could be easily dissolved in the lumen of the intestine. In conclusion, γ-CD inclusion complex is an appropriate formulation for supplying RLA as a drug or nutritional supplement with respect to absorption.
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: Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan. gan.ln284@gmail.com.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Iwamoto
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan. j3a08085@ed.noda.tus.ac.jp.
authors.forename: Suetada
authors.initials: S
authors.lastname: Nagayama
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan. miyajima@my-pharm.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
authors.affiliation: CycloChem Bio Co., Ltd., KIBC654R 5-5-2 Minatojima-minamimachi Chuo-ku, Kobe 650-0047, Japan. naoko.ikuta@people.kobe-u.ac.jp.|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: 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. hiroshi.fukumi@cyclochem.com.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukumi
authors.affiliation: CycloChem Bio Co., Ltd., KIBC654R 5-5-2 Minatojima-minamimachi Chuo-ku, Kobe 650-0047, 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; D007408:Intestinal Absorption / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000008:administration & dosage / Q000378:metabolism*; D047408:gamma-Cyclodextrins / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D047408:gamma-Cyclodextrins; D008063:Thioctic Acid; C023792:gamma-cyclodextrin