Preclinical Pharmacokinetics of Lamivudine and Its Interaction with <i>Schisandra chinensis</i> Extract in Rats

Li, Chi Lin; Hsieh, Ching‐Chuan; Tsai, Tung Hu

doi:10.1021/acsomega.9b03922

Cited by 4 publications

(3 citation statements)

References 36 publications

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“…Rats were dosed with 10 mg/kg NBMPR-P, the phosphorylated prodrug of NBMPR, or vehicle 20 minutes before 10 mg/kg clofarabine, 10 mg/kg lamivudine, or vehicle dosing. These clofarabine and lamivudine doses were sufficient to detect within the testes and were well-within the dose ranges of previously published studies (Arthaud and Seals, 2007;Bonate et al, 2005;Li et al, 2020;U.S. Food and Drug Administration, 2003;U.S.…”

Section: Rodent Modelssupporting

confidence: 84%

In Vitro and In Vivo Models for Drug Transport Across the Blood-Testis Barrier

2023

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The blood-testis barrier (BTB) is a selectively permeable membrane barrier formed by adjacent Sertoli cells (SCs) in the seminiferous tubules of the testes that develops intercellular junctional complexes to protect developing germ cells from external pressures. However, due to this inherent defense mechanism, the seminiferous tubule lumen can act as a pharmacological sanctuary site for latent viruses (e.g., Ebola, Zika) and cancers (e.g., leukemia). Therefore, it is critical to identify and evaluate BTB carrier-mediated drug delivery pathways to successfully treat these viruses and cancers. Many drugs are unable to effectively cross cell membranes without assistance from carrier proteins like transporters because they are large, polar, and often carry a charge at physiological pH. SCs express transporters that selectively permit endogenous compounds, such as carnitine or nucleosides, across the BTB to support normal physiological activity, although reproductive toxicants can also use these pathways, thereby circumventing the BTB. Certain xenobiotics, including select cancer therapeutics, antivirals, contraceptives, and environmental toxicants, are known to accumulate within the male genital tract and cause testicular toxicity; however, the transport pathways by which these compounds circumvent the BTB are largely unknown. Consequently, there is a need to identify the clinically relevant BTB transport pathways in in vitro and in vivo BTB models that recapitulate human pharmacokinetics and pharmacodynamics for these xenobiotics. This review summarizes the various in vitro and in vivo models of the BTB reported in the literature and highlights the strengths and weaknesses of certain models for drug disposition studies.

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Section: Rodent Modelssupporting

confidence: 84%

In Vitro and In Vivo Models for Drug Transport Across the Blood-Testis Barrier

2023

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“…Baill is cultivated in northeastern China, Korea, and Japan. As a traditional Chinese herb, it has been used as an antitussive and for the treatment of insomnia and hepatitis 18–20 . Recent studies have shown that the extracts of Schisandra possess biological activities, including anticancer, antioxidant, neuroprotective, hepatoprotective and anti‐inflammatory activities 21 .…”

Section: Introductionmentioning

confidence: 99%

“…As a traditional Chinese herb, it has been used as an antitussive and for the treatment of insomnia and hepatitis. 18 , 19 , 20 Recent studies have shown that the extracts of Schisandra possess biological activities, including anticancer, antioxidant, neuroprotective, hepatoprotective and anti‐inflammatory activities. 21 In addition, studies have reported that the Schisandra leaf extract relieves pain and inflammation in a rat model of OA.…”

Section: Introductionmentioning

confidence: 99%

Schisandra extract ameliorates arthritis pathogenesis by suppressing the NF‐κB and MAPK signalling pathways

Han

Lee

Nam

et al. 2023

J Cellular Molecular Medi

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Schisandra chinensis is a medicinal plant used to treat various diseases. Extracts from the leaves or fruits of S. chinensis and their components are used in osteoarthritis (OA). The OA inhibitory effect of schisandrol A, one of its components, has been previously confirmed. We aimed to confirm the OA inhibitory effect of Schisandra (including components like schisandrol A) to identify why the inhibitory effect of the Schisandra extract is better. First, we investigated the effects of the Schisandra extract on OA as a potential therapeutic. Experimental OA was induced in a mouse model via destabilized medial meniscus surgery. The animals were orally administered the Schisandra extract; the inhibition of cartilage destruction was confirmed using histological analysis. In vitro analysis showed that the Schisandra extract attenuated osteoarthritic cartilage destruction by regulating IL‐1β‐induced MMP3 and COX‐2 levels. The Schisandra extract inhibited IL‐1β‐induced degradation of IκB (NF‐κB pathway) and IL‐1β‐induced phosphorylation of p38 and JNK (mitogen‐activated protein kinase (MAPK) pathway). RNA‐sequencing analysis showed that the Schisandra extract decreased the expression of IL‐1β‐induced MAPK and NF‐κB signalling pathway‐related genes more than schisandrol A alone. Therefore, Schisandra extract may be more effective than schisandrol A in preventing OA progression by regulating MAPK and NF‐κB signalling.

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Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics

Chen¹,

Wang²,

Song³

et al. 2021

IJN

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Antiviral drugs (AvDs) are the primary resource in the global battle against viruses, including the recent fight against corona virus disease 2019 . Most AvDs require multiple medications, and their use frequently leads to drug resistance, since they have poor oral bioavailability and low efficacy due to their low solubility/low permeability. Characterizing the in vivo metabolism and pharmacokinetic characteristics of AvDs may help to solve the problems associated with AvDs and enhance their efficacy. In this review of AvDs, we systematically investigated their structure-based metabolic reactions and related enzymes, their cellular pharmacology, and the effects of metabolism on AvD pharmacodynamics and pharmacokinetics. We further assessed how delivery systems achieve better metabolism and pharmacology of AvDs. This review suggests that suitable nanosystems may help to achieve better pharmacological activity and pharmacokinetic behavior of AvDs by altering drug metabolism through the utilization of advanced nanotechnology and appropriate administration routes. Notably, such AvDs as ribavirin, remdesivir, favipiravir, chloroquine, lopinavir and ritonavir have been confirmed to bind to the severe acute respiratory syndrome-like coronavirus (SARS-CoV-2) receptor and thus may represent anti-COVID-19 treatments. Elucidating the metabolic and pharmacokinetic characteristics of AvDs may help pharmacologists to identify new formulations with high bioavailability and efficacy and help physicians to better treat virus-related diseases, including COVID-19.

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Preclinical Pharmacokinetics of Lamivudine and Its Interaction with Schisandra chinensis Extract in Rats

Cited by 4 publications

References 36 publications

In Vitro and In Vivo Models for Drug Transport Across the Blood-Testis Barrier

In Vitro and In Vivo Models for Drug Transport Across the Blood-Testis Barrier

Schisandra extract ameliorates arthritis pathogenesis by suppressing the NF‐κB and MAPK signalling pathways

Antiviral Drug Delivery System for Enhanced Bioactivity, Better Metabolism and Pharmacokinetic Characteristics

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