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  1. Article ; Online: Pharmacokinetic analysis of placental transfer of ritonavir as a component of paxlovid using microdialysis in pregnant rats

    Chung-Kai Sun / Wan-Hsin Lee / Muh-Hwa Yang / Tung-Hu Tsai

    Heliyon, Vol 10, Iss 2, Pp e24333- (2024)

    2024  

    Abstract: Background: Ritonavir is one of the most potent CYP3A4 inhibitor currently on the market, and is often used together with other antiviral drugs to increase their bioavailability and efficacy. Paxlovid, consisting of nirmatrelvir and ritonavir, was ... ...

    Abstract Background: Ritonavir is one of the most potent CYP3A4 inhibitor currently on the market, and is often used together with other antiviral drugs to increase their bioavailability and efficacy. Paxlovid, consisting of nirmatrelvir and ritonavir, was approved for the treatment of COVID-19. As previous studies regarding the use of ritonavir during pregnancy were limited to ex-vivo experiments and systemic safety data, to fully explore the detailed pharmacokinetics of ritonavir in pregnant rats’ blood and conceptus, an analytical method consisted of multi-microdialysis coupled with UHPLC-MS/MS were developed to analyze the pharmacokinetics of ritonavir, both as a component of Paxlovid and by itself. 17 days pregnant female Sprague-Dawley rats were randomly split into three experimental group: normal dosage of ritonavir alone (7 mg kg−1), normal dosage of Paxlovid (ritonavir 7 mg kg−1 + nirmatrelvir 15 mg kg−1), and 3× dosage of ritonavir (21 mg kg−1). Results: 3× dosage of ritonavir produced a more than 3× increase in rats’ blood and placenta. Transfer rate of ritonavir to the placenta, amniotic fluid, and fetus were determined to be 20.7%, 13.8%, and 4.7% respectively. Concentration of ritonavir in the placenta, amniotic fluid, and fetus did not significantly go down after 8 h. Significance: Overall, ritonavir's metabolism was not influenced by the presence of nirmatrelvir in pregnant rats. A 3× increase in dosage produced a concentration of roughly 4×, most likely a result of ritonavir's auto-inhibition effect on cytochrome P450 proteins. Accumulation of ritonavir is possible in placenta, amniotic fluid, and fetus.
    Keywords Microdialysis ; Ritonavir ; Paxlovid ; Pharmacokinetic ; Pregnancy ; Placenta barrier ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
    Subject code 610
    Language English
    Publishing date 2024-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Preclinical Herb–Drug Pharmacokinetic Interaction of Panax ginseng Extract and Selegiline in Freely Moving Rats

    Ling Yang / Chi-Lin Li / Tung-Hu Tsai

    ACS Omega, Vol 5, Iss 9, Pp 4682-

    2020  Volume 4688

    Keywords Chemistry ; QD1-999
    Language English
    Publishing date 2020-02-01T00:00:00Z
    Publisher American Chemical Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Scanning Electron Microscopy and Liquid Chromatography for Physical and Chemical Inspection of Industrial Pharmaceutical Traditional Chinese Herbal Medicine

    Wen-Ya Peng / Tung-Hu Tsai

    ACS Omega, Vol 5, Iss 20, Pp 11563-

    2020  Volume 11569

    Keywords Chemistry ; QD1-999
    Language English
    Publishing date 2020-05-01T00:00:00Z
    Publisher American Chemical Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Preclinical study of simultaneous pharmacokinetic and pharmacodynamic herb-drug interactions between Yin-Chen-Hao-Tang and spironolactone

    Tun-Pin Hsueh / Tung-Hu Tsai

    BMC Complementary Medicine and Therapies, Vol 20, Iss 1, Pp 1-

    2020  Volume 9

    Abstract: Abstract Background The prevalence and therapeutic effects of the use of herbal remedies for chronic liver diseases make the combined administration of herbal products with conventional treatment unable to be ignored. This study investigated the ... ...

    Abstract Abstract Background The prevalence and therapeutic effects of the use of herbal remedies for chronic liver diseases make the combined administration of herbal products with conventional treatment unable to be ignored. This study investigated the pharmacokinetic and pharmacodynamic herb-drug interactions between the herbal formula Yin-Chen-Hao-Tang (YCHT) and spironolactone. Methods A selective high-performance liquid chromatography (HPLC) method was developed and validated for the detection of spironolactone and its metabolite canrenone in rat urine. The interaction study was conducted by collecting urine samples after oral administration of spironolactone alone or in combination with YCHT for 5 days. Urine pharmacokinetic parameters and urinary sodium, potassium, volume, and weight were analyzed. Results The results revealed significant increases in the cumulative amount and the area under the rate curve (AURC) of the metabolite canrenone after pretreatment with the high dose of YCHT. The urine weight and volume were significantly reduced dose-dependently as a result of pretreatment with YCHT. The urinary sodium-to-potassium ratio, which indicates diuretic effects, was also reduced in the high-dose YCHT condition. Conclusions Herb-drug pharmacokinetic and pharmacodynamic interactions between YCHT and spironolactone were observed in the study. The herb-drug interaction that appeared with a single dose of spironolactone should be considered when patients are being treated with a continuous administration of this drug.
    Keywords Artemisia ; Drug interaction ; Herbal medicine ; Spironolactone ; Liver disease ; Other systems of medicine ; RZ201-999
    Subject code 610
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Preclinical Pharmacokinetic Interaction and Histopathological Analyses of Hedyotis diffusa on Sorafenib in Rats

    Chin-Tsung Ting / Yung-Yi Cheng / Tung-Hu Tsai

    ACS Omega, Vol 6, Iss 4, Pp 3060-

    2021  Volume 3067

    Keywords Chemistry ; QD1-999
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher American Chemical Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Biotransformation and transplacental transfer of the anti-viral remdesivir and predominant metabolite, GS-441524 in pregnant rats

    Ling Yang / I-Hsin Lin / Lie-Chwen Lin / Jeffrey W. Dalley / Tung-Hu Tsai

    EBioMedicine, Vol 81, Iss , Pp 104095- (2022)

    2022  

    Abstract: Summary: Background: Remdesivir was the first prodrug approved to treat coronavirus disease 2019 (COVID-19) and has the potential to be used during pregnancy. However, it is not known whether remdesivir and its main metabolite, GS-441524 have the ... ...

    Abstract Summary: Background: Remdesivir was the first prodrug approved to treat coronavirus disease 2019 (COVID-19) and has the potential to be used during pregnancy. However, it is not known whether remdesivir and its main metabolite, GS-441524 have the potential to cross the blood-placental barrier. We hypothesize that remdesivir and predominant metabolite GS-441524may cross the blood-placental barrier to reach the embryo tissues. Methods: To test this hypothesis, ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) coupled with multisite microdialysis was used to monitor the levels of remdesivir and the nucleoside analogue GS-441524 in the maternal blood, fetus, placenta, and amniotic fluid of pregnant Sprague-Dawley rats. The transplacental transfer was evaluated using the pharmacokinetic parameters of AUC and mother-to-fetus transfer ratio (AUCfetus/AUCmother). Findings: Our in-vivo results show that remdesivir is rapidly biotransformed into GS-441524 in the maternal blood, which then readily crossed the placenta with a mother-to-fetus transfer ratio of 0.51 ± 0.18. The Cmax and AUClast values of GS-441524 followed the order: maternal blood > amniotic fluid > fetus > placenta in rats. Interpretation: While remdesivir does not directly cross into the fetus, however, its main metabolite, GS-441524 readily crosses the placenta and can reside there for at least 4 hours as shown in the pregnant Sprague-Dawley rat model. These findings suggest that careful consideration should be taken for the use of remdesivir in the treatment of COVID-19 in pregnancy. Funding: Ministry of Science and Technology of Taiwan.
    Keywords Remdesivir ; GS-441524 ; Microdialysis ; Blood-placental barrier ; Pharmacokinetics ; Medicine ; R ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Local Liver Irradiation Concurrently Versus Sequentially with Cabozantinib on the Pharmacokinetics and Biodistribution in Rats

    Yu-Chuen Huang / Pei-Ying Hsieh / Li-Ying Wang / Tung-Hu Tsai / Yu-Jen Chen / Chen-Hsi Hsieh

    International Journal of Molecular Sciences, Vol 24, Iss 5849, p

    2023  Volume 5849

    Abstract: The aim of this study was to evaluate the radiotherapy (RT)-pharmacokinetics (PK) effect of cabozantinib in concurrent or sequential regimens with external beam radiotherapy (EBRT) or stereotactic body radiation therapy (SBRT). Concurrent and sequential ... ...

    Abstract The aim of this study was to evaluate the radiotherapy (RT)-pharmacokinetics (PK) effect of cabozantinib in concurrent or sequential regimens with external beam radiotherapy (EBRT) or stereotactic body radiation therapy (SBRT). Concurrent and sequential regimens involving RT and cabozantinib were designed. The RT–drug interactions of cabozantinib under RT were confirmed in a free-moving rat model. The drugs were separated on an Agilent ZORBAX SB-phenyl column with a mobile phase consisting of 10 mM potassium dihydrogen phosphate (KH 2 PO 4 )–methanol solution (27:73, v / v ) for cabozantinib. There were no statistically significant differences in the concentration versus time curve of cabozantinib (AUC cabozantinib ) between the control group and the RT 2Gy×3 f’x and RT 9Gy×3 f’x groups in the concurrent and the sequential regimens. However, compared to those in the control group, the T max , T 1/2 and MRT decreased by 72.8% ( p = 0.04), 49.0% ( p = 0.04) and 48.5% ( p = 0.04) with RT 2Gy×3 f’x in the concurrent regimen, respectively. Additionally, the T 1/2 and MRT decreased by 58.8% ( p = 0.01) and 57.8% ( p = 0.01) in the concurrent RT 9Gy×3 f’x group when compared with the control group, respectively. The biodistribution of cabozantinib in the heart increased by 271.4% ( p = 0.04) and 120.0% ( p = 0.04) with RT 2Gy×3 f’x in the concurrent and sequential regimens compared to the concurrent regimen, respectively. Additionally, the biodistribution of cabozantinib in the heart increased by 107.1% ( p = 0.01) with the RT 9Gy×3 f’x sequential regimen. Compared to the RT 9Gy×3 f’x concurrent regimen, the RT 9Gy×3 f’x sequential regimen increased the biodistribution of cabozantinib in the heart (81.3%, p = 0.02), liver (110.5%, p = 0.02), lung (125%, p = 0.004) and kidneys (87.5%, p = 0.048). No cabozantinib was detected in the brain in any of the groups. The AUC of cabozantinib is not modulated by irradiation and is not affected by treatment strategies. However, the biodistribution of cabozantinib in the heart is ...
    Keywords biodistribution ; cabozantinib ; hepatocellular carcinoma ; pharmacokinetics ; radiotherapy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 290
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Anti-Cancer Effects of Oxygen-Atom-Modified Derivatives of Wasabi Components on Human Leukemia Cells

    Jui-Feng Lin / Chih-Wen Chi / Yu-Chuen Huang / Tung-Hu Tsai / Yu-Jen Chen

    International Journal of Molecular Sciences, Vol 24, Iss 6823, p

    2023  Volume 6823

    Abstract: 1-Isothiocyanato-6-(methylsulfinyl)-hexanate (6-MITC) is a natural compound found in Wasabia japonica . The synthetic derivatives 1-Isothiocyanato-6-(methylsulfenyl)-hexane (I7447) and 1-Isothiocyanato-6-(methylsulfonyl)-hexane (I7557) were obtained from ...

    Abstract 1-Isothiocyanato-6-(methylsulfinyl)-hexanate (6-MITC) is a natural compound found in Wasabia japonica . The synthetic derivatives 1-Isothiocyanato-6-(methylsulfenyl)-hexane (I7447) and 1-Isothiocyanato-6-(methylsulfonyl)-hexane (I7557) were obtained from 6-MITC by deleting and adding an oxygen atom to the sulfone group, respectively. We previously demonstrated that extensive mitotic arrest, spindle multipolarity, and cytoplasmic vacuole accumulation were induced by 6-MITC and inhibited the viability of human chronic myelogenous leukemia K562 cells. In this study, we examined the anti-cancer effects of 6-MITC derivatives on human chronic myelogenous leukemia (CML) cells. Autophagy was identified as the formation of autophagosomes with double-layered membranes using transmission electron microscopy. Cell cycle and differentiation were analyzed using flow cytometry. Apoptosis was detected by annexin V staining. After treatment with I7447 and I7557, the G2/M phase of cell cycle arrest was revealed. Cell death can be induced by a distinct mechanism (the simultaneous occurrence of autophagy and aberrant mitosis). The expression levels of acridine orange were significantly affected by lysosomal inhibitors. The natural wasabi component, 6-MITC, and its synthetic derivatives have similar effects on human chronic myelogenous leukemia cells and may be developed as novel therapeutic agents against leukemia.
    Keywords wasabi ; 6-(methylsulfinyl)hexyl isothiocyanate ; 6-(methylsulfenyl)hexyl isothiocyanate ; 6-(methylsulfonyl)hexyl isothiocyanate ; mitosis ; autophagy ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2023-04-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Enterohepatic Circulation and Pharmacokinetics of Genistin and Genistein in Rats

    Ya-Yu Yang / Tung-Hu Tsai

    ACS Omega, Vol 4, Iss 19, Pp 18428-

    2019  Volume 18433

    Keywords Chemistry ; QD1-999
    Language English
    Publishing date 2019-10-01T00:00:00Z
    Publisher American Chemical Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article ; Online: Preclinical Pharmacokinetics of Lamivudine and Its Interaction with Schisandra chinensis Extract in Rats

    Chi-Lin Li / Chen-Hsi Hsieh / Tung-Hu Tsai

    ACS Omega, Vol 5, Iss 4, Pp 1997-

    2020  Volume 2004

    Keywords Chemistry ; QD1-999
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher American Chemical Society
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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