Effect of γ-Cyclodextrin Inclusion Complex on the Absorption of R-α-Lipoic Acid in Rats
Abstract
:1. Introduction
2. Results
2.1. Absorption after Oral Administration of RLA and Its CD Inclusion Complexes
Formulation | RLA | RLA/α-CD | RLA/β-CD | RLA/γ-CD | RLA-Na |
---|---|---|---|---|---|
Route | po | po | po | po | iv |
Dose as amount of RLA (mg/kg) | 20 | 20 | 20 | 20 | 5 |
Cmax or C0 (µg/mL) | 1.7 ± 0.9 | 1.4 ± 0.6 | 1.6 ± 1.9 | 3.4 ± 2.5 | 19.5 ± 3.3 |
Tmax (min) | 11.8 ± 14.1 | 10.7 ± 10.7 | 33.3 ± 44.0 | 9.0 ± 10.7 | not determined |
AUC0-t (µg·min/mL) | 56 ± 35 * | 56 ± 12 * | 50 ± 19 * | 121 ± 24 | 96 ± 19 |
AUCpo/AUCiv (%) | 14.6 | 14.6 | 13 | 31.5 | not calculated |
2.2. Absorption Site of RLA after Administration as RLA/γ-CD
Formulation | RLA | RLA/γ-CD | RLA | RLA/γ-CD |
---|---|---|---|---|
Route | po under PL | po under PL | id | id |
Group number | 1 | 2 | 3 | 4 |
Cmax (µg/mL) | 1.1 ± 0.4 *, a,b | 1.3 ± 0.6 *, c,d | 5.4 ± 0.6 *, a,c,e | 14.9 ± 3.9 *, b,d,e |
Tmax (min) | 5.7 ± 4.4 | 2.5 ± 1.1 | 1.7 ± 0.5 | 5.2 ± 2.6 |
AUC0–t (µg·min/mL) | 32 ± 14 *, b | 33 ± 16 *, d | 46 ± 15 *, e | 235 ± 45 *, b,d,e |
2.3. Effects of Bile Acid, α-Amylase, and Dissolution on RLA Absorption after Administration as RLA/γ-CD
Formulation | RLA | RLA/γ-CD | RLA | RLA/γ-CD | RLA-Na | RLA-Na |
---|---|---|---|---|---|---|
Route | id | id | id | id | iv | iv |
Group number | 1 | 2 | 3 | 4 | not determined | not determined |
Operation | Sham | Sham | BDL | BDL | Sham | BDL |
Cmax or C0 (µg/mL) | 5.7 ± 0.8 *,a,b | 16.9 ± 5.2 *,a,c | 5.8 ± 1.7 *,c,b | 11.9 ± 3.5 *,b,d | 79.4 ± 20.9 | 79.2 ± 10.9 |
Tmax (min) | 1.8 ± 0.4 *,b | 5.2 ± 2.9 | 1.8 ± 0.4 *,b | 6.2 ± 3.2 *,b,d | not determined | not determined |
AUC0–t (µg·min/mL) | 49 ± 16 *,a,b | 260 ± 50 *,a,c | 54 ± 17 *,c,d | 259 ± 55 *,b,d | 516 ± 87 | 540 ± 79 |
Formulation | RLA | RLA/γ-CD | RLA | RLA/γ-CD | RLA-Na |
---|---|---|---|---|---|
Route | id | id | id | id | id |
Group number | 1 | 2 | 3 | 4 | 5 |
Combined-drug | Nothing | Nothing | Acarbose | Acarbose | Nothing |
Cmax (µg/mL) | 7.0 ± 2.1 *,a,b,c | 17.1 ± 4.3 *,a,d | 8.3 ± 1.9 *,d,e | 14.6 ± 7.2 *,b,f | 23.8 ± 1.2 *,c,e,f |
Tmax (min) | 1.8 ± 0.4 *,c | 2.8 ± 1.7 | 3.5 ± 1.6 | 2.5 ± 1.2 | 4.5 ± 1.2 *,c |
AUC0-t (µg·min/mL) | 49 ± 10 *,a,b,c | 234 ± 47 *,a,d | 76 ± 20 *,d,e,g | 210 ± 57 *,b,g | 245 ± 24 *,c,e |
2.4. X-ray Imaging
3. Discussion
4. Experimental Section
4.1. Chemicals and Reagents
4.2. Animals
4.3. Drug Administration
4.4. Bile Duct Ligation
4.5. Assay of α-Amylase Activity in the Intestinal Lumen
4.6. Blood Collection
4.7. Determination of Plasma RLA Concentration by LC-MS/MS
4.8. X-ray Imaging
4.9. Measurement of Viscosity
4.10. Pharmacokinetics Analysis
4.11. Statistical Analysis
5. Conclusions
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Uchida, R.; Iwamoto, K.; Nagayama, S.; Miyajima, A.; Okamoto, H.; Ikuta, N.; Fukumi, H.; Terao, K.; Hirota, T. Effect of γ-Cyclodextrin Inclusion Complex on the Absorption of R-α-Lipoic Acid in Rats. Int. J. Mol. Sci. 2015, 16, 10105-10120. https://doi.org/10.3390/ijms160510105
Uchida R, Iwamoto K, Nagayama S, Miyajima A, Okamoto H, Ikuta N, Fukumi H, Terao K, Hirota T. Effect of γ-Cyclodextrin Inclusion Complex on the Absorption of R-α-Lipoic Acid in Rats. International Journal of Molecular Sciences. 2015; 16(5):10105-10120. https://doi.org/10.3390/ijms160510105
Chicago/Turabian StyleUchida, Ryota, Kosuke Iwamoto, Suetada Nagayama, Atsushi Miyajima, Hinako Okamoto, Naoko Ikuta, Hiroshi Fukumi, Keiji Terao, and Takashi Hirota. 2015. "Effect of γ-Cyclodextrin Inclusion Complex on the Absorption of R-α-Lipoic Acid in Rats" International Journal of Molecular Sciences 16, no. 5: 10105-10120. https://doi.org/10.3390/ijms160510105