Plasma Pharmacokinetics and Tissue Distribution of Doxorubicin in Rats following Treatment with Astragali Radix
Doxorubicin (DOX) is an essential component in chemotherapy, and Astragali Radix (AR) is a widely used tonic herbal medicine. The combination of DOX and AR offers widespread, well-documented advantages in treating cancer, e.g., reducing the risk of adverse effects. This study mainly aims to uncover...
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| Main Authors: | , , , , , , |
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| Format: | Book |
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MDPI AG,
2022-09-01T00:00:00Z.
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| Summary: | Doxorubicin (DOX) is an essential component in chemotherapy, and Astragali Radix (AR) is a widely used tonic herbal medicine. The combination of DOX and AR offers widespread, well-documented advantages in treating cancer, e.g., reducing the risk of adverse effects. This study mainly aims to uncover the impact of AR on DOX disposition in vivo. Rats received a single intravenous dose of 5 mg/kg DOX following a single-dose co-treatment or multiple-dose pre-treatment of AR (10 g/kg × 1 or × 10). The concentrations of DOX in rat plasma and six tissues, including heart, liver, lung, kidney, spleen, and skeletal muscle, were determined by a fully validated LC-MS/MS method. A network-based approach was further employed to quantify the relationships between enzymes that metabolize and transport DOX and the targets of nine representative AR components in the human protein-protein interactome. We found that short-term (≤10 d) AR administration was ineffective in changing the plasma pharmacokinetics of DOX in terms of the area under the concentration-time curve (AUC, 1303.35 ± 271.74 μg/L*h versus 1208.74 ± 145.35 μg/L*h, <i>p</i> > 0.46), peak concentrations (C<sub>max</sub>, 1351.21 ± 364.86 μg/L versus 1411.01 ± 368.38 μg/L, <i>p</i> > 0.78), and half-life (t<sub>1/2</sub>, 31.79 ± 5.12 h versus 32.05 ± 6.95 h, <i>p</i> > 0.94), etc. Compared to the isotype control group, DOX concentrations in six tissues slightly decreased under AR pre-administration but only showed statistical significance (<i>p</i> < 0.05) in the liver. Using network analysis, we showed that five of the nine representative AR components were not localized to the vicinity of the DOX disposition-associated module. These findings suggest that AR may mitigate DOX-induced toxicity by affecting drug targets rather than drug disposition. |
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| Item Description: | 10.3390/ph15091104 1424-8247 |