Determination and prediction of permeability across intestinal epithelial cell monolayer of a diverse range of industrial chemicals/drugs for estimation of oral absorption as a putative marker of hepatotoxicity

Kamiya, Yusuke; Takaku, Hiroka; Yamada, Rio; Akase, Chisato; Abe, Yuto; Sekiguchi, Yoshinori; Murayama, Norie; Shimizu, Makiko; Kitajima, Masato; Shono, Fumiaki; Funatsu, Kimito; Yamazaki, Hiroshi

doi:10.1016/j.toxrep.2020.01.004

Cited by 44 publications

(26 citation statements)

References 31 publications

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“…According to the literature, values from 0 to 20% for poorly absorbed molecules are considered for the evaluation of permeability and intestinal absorption. From 20 to 70% for molecules with moderately absorbed molecules and from 70 to 100% for well absorbed molecules ( Al-Heibshy et al., 2020 ; Kamiya et al., 2020 ; Yee, 1997 ). Our results in silico for the rose oxide predict a percentage of human intestinal absorption (AIH%) of 100%, which demonstrates that the substance is able to be completely absorbed by the intestine.…”

Section: Discussionmentioning

confidence: 99%

Antidepressant activity of rose oxide essential oil: possible involvement of serotonergic transmission

Maia

Andrade

Filgueiras

et al. 2021

Heliyon

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Rose oxide (RO) is a monoterpene found in rose oil fragrances. This monoterpene has been reported to possess anti-inflammatory activity, however, little is known regarding its pharmacological activity. The present study was carried out to evaluate its antidepressant action and possible mechanisms of action. Analysis of ADMET pharmacokinetic properties (absorption, distribution, metabolism, excretion and toxicity) of rose oxide was performed by computational prediction analysis. Behavioral tests were performed to assess the interaction between rose oxide and the central nervous system and antidepressant effect that includes: forced swim test (FST), tail suspension test (TST), open field test (OFT) and rota-rod test. The results of pharmacokinetic and toxicological properties indicate that rose oxide could be used orally, since it has good intestinal absorption as well as pharmacological and toxicological properties that can be similar to pharmacological compounds (regular hepatic metabolism and low toxicity). Treatment with 50 mg/kg of rose oxide was able to decrease the immobility time of animals not affected by FST and TST and was not able to alter the motor activity of the OFT and rota-rod test, suggesting modulation and antidepressant activity. Docking data suggest that rose oxide can bind to receptors in the serotonergic pathway. The results described here suggest that rose oxide has antidepressant activity, modulating the serotonergic pathway.

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Section: Discussionmentioning

confidence: 99%

Antidepressant activity of rose oxide essential oil: possible involvement of serotonergic transmission

Maia

Andrade

Filgueiras

et al. 2021

Heliyon

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“…Heterocyclic molecules containing the benzothiazole group have shown to be more promising drug candidates to treat infectious diseases, reinforcing the pharmacological potential of benzothiazole-containing molecules (Papadopoulou et al, 2013 ). It has been reported that molecules containing thalidomide group in its structure, as those of series F , presented high hepatotoxic potential (Kamiya et al, 2020 ). In this regard, only the derivatives A7 , A8 , B5 , E35 , E38 , E39 , and E40 ( Figure 2 ) showed good pharmacokinetic and toxicological profiles, and were therefore chosen for molecular docking.…”

Section: Resultsmentioning

confidence: 99%

Identification of 1,2,3-triazole-phthalimide derivatives as potential drugs against COVID-19: a virtual screening, docking and molecular dynamic study

Holanda

Lima

Silva

et al. 2021

Journal of Biomolecular Structure and Dynamics

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In this work we aimed to perform an in silico predictive screening, docking and molecular dynamic study to identify 1,2,3-triazole-phthalimide derivatives as drug candidates against SARS-CoV-2. The in silico prediction of pharmacokinetic and toxicological properties of hundred one 1,2,3-triazole-phtalimide derivatives, obtained from SciFinderV R library, were investigated. Compounds that did not show good gastrointestinal absorption, violated the Lipinski's rules, proved to be positive for the AMES test, and showed to be hepatotoxic or immunotoxic in our ADMET analysis, were filtered out of our study. The hit compounds were further subjected to molecular docking on SARS-CoV-2 target proteins. The ADMET analysis revealed that 43 derivatives violated the Lipinski's rules and 51 other compounds showed to be positive for the toxicity test. Seven 1,2,3-triazole-phthalimide derivatives (A7, A8, B05, E35, E38, E39, and E40) were selected for molecular docking and MFCC-ab initio analysis. The results of molecular docking pointed the derivative E40 as a promising compound interacting with multiple target proteins of SARS-CoV-2. The complex E40-M pro was found to have minimum binding energy of À10.26 kcal/mol and a general energy balance, calculated by the quantum mechanical analysis, of À8.63 eV. MD simulation and MMGBSA calculations confirmed that the derivatives E38 and E40 have high binding energies of À63.47 ± 3 and À63.31 ± 7 kcal/mol against SARS-CoV-2 main protease. In addition, the derivative E40 exhibited excellent interaction values and inhibitory potential against SAR-Cov-2 main protease and viral nucleocapsid proteins, suggesting this derivative as a potent antiviral for the treatment and/or prophylaxis of COVID-19.

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“…Generally, gastric lavage and administration of charcoal are recommended within 1 h of overdose in clinical practice. In a case report [ 28 ], it was reported that gastric lavage could be effective when some medicine remained in the stomach. Activated charcoal reportedly prevents the absorption of controlled-release duloxetine tablets at 1 h after administration [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of duloxetine self-administered in overdose with quetiapine and other antipsychotic drugs in a Japanese patient admitted to hospital

Adachi

Beppu

Nishiyama

et al. 2021

J Pharm Health Care Sci

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Background Combinations of antidepressant duloxetine (at doses of 40–60 mg/day) and other antipsychotics are frequently used in clinical treatment; however, several fatal and nonfatal cases of duloxetine overdose have been documented. We experienced a patient who had taken an overdose of duloxetine (780 mg) in combination with other drugs in a suicide attempt. Case presentation The patient was a 37-year-old man (body weight, 64 kg) with a history of gender identity disorder and depression. He intentionally took an overdose of duloxetine in combination with three other antipsychotic drugs (18 mg flunitrazepam, 850 mg quetiapine, and 1100 mg trazodone) and was emergently admitted to Kyoto Medical Center. The patient’s plasma concentration of duloxetine during ambulance transport was 57 ng/ml, and the level was still as high as 126 ng/mL at 32 h after administration. Duloxetine disappeared most slowly from plasma, in contrast to quetiapine, which was the fastest to clear among the four medicines determined in this patient. The observed concentrations of duloxetine in this overdose patient were generally within the 95% confidence intervals of the plasma concentration curves predicted using a physiologically based pharmacokinetic (PBPK) model. Conclusion Even if more than 1 h (the generally recommended period) has passed after administration of duloxetine in such overdose cases, gastric lavage and/or administration of activated charcoal may be effective in clinical practice up to 6 h because of the typically slow elimination behavior illustrated by the PBPK model. Pharmacokinetic profiles visualized using PBPK modeling can inform treatment decisions in cases of drug overdose for medicines such as duloxetine in emergency clinical practice.

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Determination and prediction of permeability across intestinal epithelial cell monolayer of a diverse range of industrial chemicals/drugs for estimation of oral absorption as a putative marker of hepatotoxicity

Cited by 44 publications

References 31 publications

Antidepressant activity of rose oxide essential oil: possible involvement of serotonergic transmission

Antidepressant activity of rose oxide essential oil: possible involvement of serotonergic transmission

Identification of 1,2,3-triazole-phthalimide derivatives as potential drugs against COVID-19: a virtual screening, docking and molecular dynamic study

Pharmacokinetics of duloxetine self-administered in overdose with quetiapine and other antipsychotic drugs in a Japanese patient admitted to hospital

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