Effect of γ-Cyclodextrin Inclusion Complex on the Absorption of R-α-Lipoic Acid in Rats

International Journal of Molecular Sciences

Hinako Okamoto¹  Hiroshi Fukumi¹  Keiji Terao¹  Takashi Hirota²  Ryota Uchida²  Suetada Nagayama²  Kosuke Iwamoto²  Atsushi Miyajima²  Naoko Ikuta³ 

[1] CycloChem Bio Co., Ltd., KIBC654R 5-5-2 Minatojima-minamimachi Chuo-ku, Kobe 650-0047, Japan;Department of Biopharmaceutics, Faculty of Pharmaceutical Science, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan;Graduate School of Medicine, Kobe University, 7-5-2 Kusunoki-cho Chuo-ku, Kobe 650-0017, Japan;

关键词: γ-cyclodextrin;    inclusion complex;    R-α-lipoic acid;    pharmacokinetic-profile;    absorption;    intraduodenal administration;    rats;    X-ray imaging;   

DOI  :  10.3390/ijms160510105

来源: DOAJ

【 摘 要 】

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 withα-, 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 theplasma 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 ofnon-inclusion RLA, and was almost comparable to the AUC after intraduodenal administration of RLA-Na solution. Furthermore, the AUC after intraduodenal administration ofRLA/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.

【 授权许可】

Unknown