| Autor: |
Li-Xiang Ye, Ying Xu, Shui-Hua Zhang, Da-Xuan Cao, Ling-Fan Chen, Yan-Ping Su, Hui-Hui Huang, Chang-Xi Yu |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
|
| Zdroj: |
Frontiers in Pharmacology, Vol 11 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
1663-9812 |
| DOI: |
10.3389/fphar.2020.01113 |
| Popis: |
Aging leads to changes in nearly all pharmacokinetic phases. Koumine (KM), an alkaloid derived from Gelsemium elegans Benth., is effective against age-associated chronic diseases, but its dose proportionality following oral administration in aged individuals remains unknown. Herein, we established and validated a simple method that requires low sample volumes to determine KM concentration in rats using ultra-performance liquid chromatography-tandem mass spectrometry. The maximum plasma concentration (Cmax) of 7 mg·kg−1 KM was ~12-fold and ~24-fold higher than that of 0.28 mg·kg−1 KM in adult and aged rats, respectively (P < 0.01). Time to reach Cmax (Tmax) for 7 mg·kg−1 KM was 4-fold longer in aged rats (P < 0.05). The area under the curve (AUC) of 7 mg·kg−1 KM was >17-fold and >43-fold higher than those of 0.28 mg·kg−1 KM in adult and aged rats, respectively (P < 0.01). The half-life (t1/2) of 7 mg·kg−1 KM was over 4-fold longer than that of 0.28 mg·kg−1 KM in adult rats (P < 0.01). The t1/2 of 1.4 and 7 mg·kg−1 KM were 1.5~2-fold longer, than that of 0.28 mg·kg−1 KM in aged rats (P < 0.05). The clearance rate of 7 mg·kg−1 KM was significantly lower in aged than in adult rats (P < 0.05). For 7.0 mg·kg−1 KM, the Cmax in aged rats was higher than in adult rats during the Tmax period (P < 0.05). In aged rats, the AUC for KM was >2.5-fold higher (P < 0.05) and the t1/2 was >60% longer than in adult rats (P < 0.05). These results help interpret the pharmacokinetics of KM in aging-associated diseases. |
| Databáze: |
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| Externí odkaz: |
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