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Planta Med 2023; 89(09): 903-915
DOI: 10.1055/a-2021-2812
Pharmacokinetic Investigations
Original Papers

Multiple Component Pharmacokinetics after Oral Administration of Gnaphalium affine Extract in Rats

Shiyi Han
State Key Lab. of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry Co., Ltd, China State Institute of Pharmaceutical Industry Co., Ltd, Shanghai, Peopleʼs Republic of China
,
Xizi Liu
State Key Lab. of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry Co., Ltd, China State Institute of Pharmaceutical Industry Co., Ltd, Shanghai, Peopleʼs Republic of China
,
Ye Chen
State Key Lab. of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry Co., Ltd, China State Institute of Pharmaceutical Industry Co., Ltd, Shanghai, Peopleʼs Republic of China
,
Junping Chen
State Key Lab. of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry Co., Ltd, China State Institute of Pharmaceutical Industry Co., Ltd, Shanghai, Peopleʼs Republic of China
,
Qinghua Han
State Key Lab. of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry Co., Ltd, China State Institute of Pharmaceutical Industry Co., Ltd, Shanghai, Peopleʼs Republic of China
,
Siyang Fan
State Key Lab. of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry Co., Ltd, China State Institute of Pharmaceutical Industry Co., Ltd, Shanghai, Peopleʼs Republic of China
› InstitutsangabenGefördert durch: Natural Science Foundation of Shanghai 15ZR1440100
Gefördert durch: Data Center of Management Science, National Natural Science Foundation of China - Peking University 81603279
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Abstract

Gnaphalium affine is traditionally used to treat hyperuricemia and gout in China. Recently, the hypouricemic and renal protective effects of G. affine extract (GAD) have been deeply evaluated. However, little is known about the pharmacokinetics (PKs) of bioactive constituents in GAD. This study is aimed at investigating the individual and holistic pharmacokinetics of 10 bioactive components (including caffeic acid, caffeoylquinic acids, and flavonoids) in rats after single and multiple administrations of GAD. GAD is orally dosed to normal male rats at doses of 225, 450, or 900 mg/kg/day for 10 consecutive days and also orally administrated to uric acid nephropathy (UAN) rats at a dose of 900 mg/kg/day for 28 consecutive days. Integrated PKs of multiple components are calculated by area under the curve (AUC)-based weighting approach. All the components show a double-peak phenomenon in terms of their plasma concentration-time curves, suggesting that the components undergo enterohepatic circulation. The integrated AUC increases in a good dose-proportional manner with GAD dose. Compared with that in normal rats, the plasma exposure of caffeic acid and caffeoylquinic acids increases by 2.3- to 4.3-fold after 10-day chronic treatment of 900 mg/kg GAD in UAN rats. Modest drug accumulation is observed after 28-day chronic treatment.

Key words

Gnaphalium affine - Asteraceae - pharmacokinetics - uric acid nephropathy - caffeoylquinic acid

Supporting Information

    The preparation of samples, UHPLC/DAD conditions, UHPLC-MS/MS conditions, detailed method validation data and supplementary PK parameters are available as Supporting Information.

  • Ergänzendes Material


Publikationsverlauf

Eingereicht: 29. September 2022

Angenommen nach Revision: 27. Januar 2023

Accepted Manuscript online:
27. Januar 2023

Artikel online veröffentlicht:
10. März 2023

© 2023. Thieme. All rights reserved.

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