Evaluation of the Effects of Astragalus membranaceus on the Pharmacokinetics of Pemetrexed Disodium and Gemcitabine in Rats by a Simple High-Performance Liquid Chromatography/UV Method
Combination therapy is opted as a potential therapeutic strategy for cancer treatment. Astragalus membranaceus combined with pemetrexed disodium or gemcitabine could reinforce the overall effects and alleviate the adverse effects. To investigate the effects of Astragalus membranaceus on the pharmaco...
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2019-01-01
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Series: | Journal of Analytical Methods in Chemistry |
Online Access: | http://dx.doi.org/10.1155/2019/3162426 |
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author | Zixuan Chu Zhiyuan Wang Teng Liu Shan Xiong Bin Liu |
author_facet | Zixuan Chu Zhiyuan Wang Teng Liu Shan Xiong Bin Liu |
author_sort | Zixuan Chu |
collection | DOAJ |
description | Combination therapy is opted as a potential therapeutic strategy for cancer treatment. Astragalus membranaceus combined with pemetrexed disodium or gemcitabine could reinforce the overall effects and alleviate the adverse effects. To investigate the effects of Astragalus membranaceus on the pharmacokinetics of pemetrexed disodium and gemcitabine, a HPLC method for simultaneous determination of pemetrexed disodium and gemcitabine in rat plasma was developed and validated. Chromatographic separation was achieved on a C18 column using a gradient mode containing water (containing 20 mM NaH2PO4 and 0.1% FA) and methanol at a flow rate of 0.8 mL/min. The specificity, linearity, recovery, stability, precision, and accuracy of the HPLC method were all validated. The rats were pretreated with Astragalus extract at the dosage of 3 g/kg for 20 consecutive days until we commence studying the pharmacokinetics of pemetrexed disodium or gemcitabine. There were no significant differences in pharmacokinetic parameters of pemetrexed disodium between the Astragalus extract treatment group and the control group. However, AUC, MRT, and Cl of gemcitabine were changed dramatically after treating with Astragalus extract (p<0.05). The AUC(0−t), AUC(0−∞), and MRT of gemcitabine decreased from 15747.12 ± 497.11 to 12312.41 ± 594.21 mg/L·min, 15976.18 ± 511.33 to 12489.59 ± 682.01 mg/L·min, and 97.83 ± 5.82 to 84.37 ± 2.79 min, respectively. The Cl of gemcitabine increased from 0.019 ± 0.0067 to 0.024 ± 0.0013 L/min/kg. The results showed that the pretreatment of Astragalus extract could exert an influence on the pharmacokinetic characteristics of gemcitabine in rats. |
format | Article |
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institution | Kabale University |
issn | 2090-8865 2090-8873 |
language | English |
publishDate | 2019-01-01 |
publisher | Wiley |
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series | Journal of Analytical Methods in Chemistry |
spelling | doaj-art-55d7446eb6d9478bada4c613c365f9392025-02-03T01:21:40ZengWileyJournal of Analytical Methods in Chemistry2090-88652090-88732019-01-01201910.1155/2019/31624263162426Evaluation of the Effects of Astragalus membranaceus on the Pharmacokinetics of Pemetrexed Disodium and Gemcitabine in Rats by a Simple High-Performance Liquid Chromatography/UV MethodZixuan Chu0Zhiyuan Wang1Teng Liu2Shan Xiong3Bin Liu4School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong 250200, ChinaThe People’s Hospital of Yucheng, Yucheng, Shandong 251200, ChinaInstitute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, ChinaInstitute of Materia Medica, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, ChinaThe People’s Hospital of Yucheng, Yucheng, Shandong 251200, ChinaCombination therapy is opted as a potential therapeutic strategy for cancer treatment. Astragalus membranaceus combined with pemetrexed disodium or gemcitabine could reinforce the overall effects and alleviate the adverse effects. To investigate the effects of Astragalus membranaceus on the pharmacokinetics of pemetrexed disodium and gemcitabine, a HPLC method for simultaneous determination of pemetrexed disodium and gemcitabine in rat plasma was developed and validated. Chromatographic separation was achieved on a C18 column using a gradient mode containing water (containing 20 mM NaH2PO4 and 0.1% FA) and methanol at a flow rate of 0.8 mL/min. The specificity, linearity, recovery, stability, precision, and accuracy of the HPLC method were all validated. The rats were pretreated with Astragalus extract at the dosage of 3 g/kg for 20 consecutive days until we commence studying the pharmacokinetics of pemetrexed disodium or gemcitabine. There were no significant differences in pharmacokinetic parameters of pemetrexed disodium between the Astragalus extract treatment group and the control group. However, AUC, MRT, and Cl of gemcitabine were changed dramatically after treating with Astragalus extract (p<0.05). The AUC(0−t), AUC(0−∞), and MRT of gemcitabine decreased from 15747.12 ± 497.11 to 12312.41 ± 594.21 mg/L·min, 15976.18 ± 511.33 to 12489.59 ± 682.01 mg/L·min, and 97.83 ± 5.82 to 84.37 ± 2.79 min, respectively. The Cl of gemcitabine increased from 0.019 ± 0.0067 to 0.024 ± 0.0013 L/min/kg. The results showed that the pretreatment of Astragalus extract could exert an influence on the pharmacokinetic characteristics of gemcitabine in rats.http://dx.doi.org/10.1155/2019/3162426 |
spellingShingle | Zixuan Chu Zhiyuan Wang Teng Liu Shan Xiong Bin Liu Evaluation of the Effects of Astragalus membranaceus on the Pharmacokinetics of Pemetrexed Disodium and Gemcitabine in Rats by a Simple High-Performance Liquid Chromatography/UV Method Journal of Analytical Methods in Chemistry |
title | Evaluation of the Effects of Astragalus membranaceus on the Pharmacokinetics of Pemetrexed Disodium and Gemcitabine in Rats by a Simple High-Performance Liquid Chromatography/UV Method |
title_full | Evaluation of the Effects of Astragalus membranaceus on the Pharmacokinetics of Pemetrexed Disodium and Gemcitabine in Rats by a Simple High-Performance Liquid Chromatography/UV Method |
title_fullStr | Evaluation of the Effects of Astragalus membranaceus on the Pharmacokinetics of Pemetrexed Disodium and Gemcitabine in Rats by a Simple High-Performance Liquid Chromatography/UV Method |
title_full_unstemmed | Evaluation of the Effects of Astragalus membranaceus on the Pharmacokinetics of Pemetrexed Disodium and Gemcitabine in Rats by a Simple High-Performance Liquid Chromatography/UV Method |
title_short | Evaluation of the Effects of Astragalus membranaceus on the Pharmacokinetics of Pemetrexed Disodium and Gemcitabine in Rats by a Simple High-Performance Liquid Chromatography/UV Method |
title_sort | evaluation of the effects of astragalus membranaceus on the pharmacokinetics of pemetrexed disodium and gemcitabine in rats by a simple high performance liquid chromatography uv method |
url | http://dx.doi.org/10.1155/2019/3162426 |
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