Prediction of the pharmacokinetics and pharmacodynamics of topiroxostat in humans by integrating the physiologically based pharmacokinetic model with the drug-target residence time model

Luo, Zhiqiang; Yang, Guohua; Han, Xing; Yang, Tingting; Ji, Yanhua; Huang, Huating; Wang, Guopeng; Yang, Liu; Sun, Wenyan

doi:10.1016/j.biopha.2019.109660

Cited by 19 publications

(12 citation statements)

References 29 publications

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“…This difference is generated due to preferential adsorption of relatively smaller particles by the grid surface of the TEM sample holder as compared to larger particles (as an instrumental error). where the value of “ n ” indicated the number experimental points repeated. The values of “FE” less than 2 can be considered as acceptable …”

Section: Methodsmentioning

confidence: 99%

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Impact of Composition and Morphology of Ketoconazole-Loaded Solid Lipid Nanoparticles on Intestinal Permeation and Gastroplus-Based Prediction Studies

et al. 2022

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Ketoconazole (KTZ) is a potential oral antifungal agent to control systemic and local infections. This study addresses the impact of composition (tween 80 and compritol as CATO) and morphology on permeation (stomach, jejunum, and ileum) profiles of KTZ-loaded solid lipid nanoparticles (SLNs) in rats followed by in vivo pharmacokinetic prediction and simulation using GastroPlus. The selected formulations were characterized for size, size distribution, zeta potential, entrapment efficiency, total drug content, morphology, in vitro drug release, ex vivo permeation and drug deposition, penetration potential, and GastroPlus-based in vivo prediction in rats. The results showed that there was considerable impact of pH, composition (CATO and tween 80), size, total drug content, and entrapment efficiency on in vitro drug release and permeation across the stomach, jejunum, and ileum. Ex vivo findings suggested pH, composition, size, and permeability coefficient-dependent permeation of SLNs across the stomach, jejunum, and ileum. Confocal laser scanning microscopy (CLSM) confirmed a relatively high degree of penetration of the optimized formulation “K-SLN4” (66.1% across the stomach, 51.5% across the jejunum, and 47.9% across the ileum) as compared to KSUS (corresponding values of 21.7%, 18.2%, and 17.4%). Finally, GastroPlus predicted in vivo dissolution/absorption as 0.012 μg/mL of K-SLN4 as compared to KSUS (the drug suspension with 0.0058 μg/mL) and a total regional absorption of 80.0% by K-SLN4 as compared to 60.1% of KSUS. There was only an impact of dose on C max (maximum plasma concentration) and area under the curve (AUC) in rats. Thus, the present strategy could be a promising alternative to parenteral and topical delivery systems for long-term therapy against systemic and local mycoses with high patient compliance.

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Section: Methodsmentioning

confidence: 99%

“…The values of "FE" less than 2 can be considered as acceptable. 13 2.2.4. In Vitro Drug Release Studies at Varied pH.…”

Section: Formulation Compositionsmentioning

confidence: 99%

Impact of Composition and Morphology of Ketoconazole-Loaded Solid Lipid Nanoparticles on Intestinal Permeation and Gastroplus-Based Prediction Studies

et al. 2022

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“…This difference is generated due to instrumental error and reported as "fold error" which should be less than 2 for acceptability. The fold error is estimated using the equation 2 (Hussain et al 2016;Luo et al 2020):…”

Section: Globular Size and Size Distribution (Pdi)mentioning

confidence: 99%

Removal of azithromycin from aqueous bulk solution using water/ethanol/transcutol/capryol-90 green nanoemulsion

Hussain

Alshehri

Altamimi

et al. 2021

Preprint

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The present work aimed to remove azithromycin (AZM) from contaminated aqueous system using a water/ethanol/transcutol/capryol-90 green nanoemulsion. The drug is identified as potential pharmaceutical drug for detrimental effect on flora and fauna of aquatic lives and human health. Green nanoemulsions were tailored and characterized for thermodynamic stability, globular size, polydispersity index (PDI), zeta potential, viscosity, refractive index (RI), and morphological assessment using transmission electron microscopy (TEM). Moreover, nanoemulsions were investigated for percent removal efficiency and factors affecting the %RE. The results obtained from in vitro characterization parameters suggested that the developed green nanoemulsions (ANE1-ANE5) were stable, and possessing globular size ˂ 200 nm. ANE5 exhibited the lowest value of globular size (49 nm), low PDI (0.17), minimum viscosity (~ 93 cP), and optimum zeta potential (-27.8 mV). The value of %RE depended upon the content of water and capryol-90 oil of the nanoemulsion. Furthermore, the value of %RE was found to be increased with increased content of water and decreased concentration of capryol-90 in the nanoemulsions. Similarly, % RE value was increased with decreased value of globular size and decreased viscosity of nanoemulsion. There was no impact of contact time on %RE results. Thus, the maximum %RE value (96.8%) was obtained by ANE5 from the aqueous solution after 20 min of contact time with ANE5. Thus, this method could be a promising approach to remove AZM from a contaminated water and suitable alternative to conventional methods.

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“…Various conventional methods (physical, chemical, and microbial) have been exploited to remove macrolide contaminants from wastewater obtained from different water resources. , These conventional methods are the least efficient (unable to remove contaminants completely from water), hectic, and costly; have a high probability of microbial growth; and are difficult to scale up for bulk cleaning . Moreover, photocatalytic degradation, Fenton reaction, UV light application, ultrasound (low frequency ultrasound ∼40 kHz), and adsorption (activated carbon) based methods are commonly used techniques for remove trace amounts of macrolides present in aquatic systems despite several limitations. − Recently, we reported green nanoemulsions as nanocarriers for removing few macrolides and anti-tubercular pharmaceuticals (clarithromycin, azithromycin, and rifampicin) contaminating aqueous solutions. − These nanoemulsions are isotropic, and thermodynamically stable, composed of water, lipid, surfactant and co-surfactant. ERN is a poorly water-soluble (0.15 mg/mL) drug as evidenced by its log P value (2.6–3.06).…”

Section: Introductionmentioning

confidence: 99%

“…The drug is a potential contaminant in aquatic systems that needs to be removed using the established economic and efficient method . There are several factors affecting the removal efficiency of the drug from contaminated water such as (a) the components (water and oil phases) of the nanoemulsion, (b) the physicochemical properties (viscosity, globular size, ferrous ions, hydrogen peroxide, and refractive index) of the nanoemulsion, (c) the degree of polluted water, (d) method efficiency, and (e) other factors (pH, UV frequency, reducing agent, microbial inhibition by antibiotics). − From the literature, it was concluded that the percent removal efficiency (%RE) of macrolides was comparatively lower than that of fluoroquinolones and the %RE values of ERN were 74 and 79% in wastewater treatment plants in Beijing and the United Kingdom (and Australia), respectively. , The drug can be estimated using previously reported methods based on the physicochemical nature of the drug. , The selection of excipients was based on various factors such as (a) the solubility of the drug, (b) the hydrophilic–lipophilic balance (HLB) value of the excipient, (c) medium-chain triglycerides capable of self-emulsification after dispersion into water, (d) capability of forming an emulsion through self-emulsification into water and subsequent adsorption of the lipophilic drug, (e) safety and biocompatibility, and (f) cost-effectiveness and ease of access. Labrafil M 1944 CS (LabM) consists chemically of mono-, di-, and triglycerides and PEG-6 (MW 300) mono- and diesters of oleic acid (C18:1) (source: Gattefossé leaflet).…”

Section: Introductionmentioning

confidence: 99%

Green Nanoemulsion Water/Ethanol/Transcutol/LabM-Based Treatment of Pharmaceutical Antibiotic Erythromycin-Contaminated Aqueous Bulk Solution

et al. 2022

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Contaminated wastewater released from hospital, domestic, and industrial sources is a major challenge to aquatic animals and human health. In this study, we addressed removal of erythromycin (ERN) from contaminated water employing water/ethanol/Transcutol/Labrafil M 1944 CS (LabM) green nanoemulsions as a nanocarrier system. ERN is a major antibiotic contaminant harming aquatic and human lives. Green nanoemulsions were prepared and evaluated for size, size distribution (measuring polydispersity index), stability, zeta potential, refractive index, and viscosity. Transmission electron microscopy (TEM) was used to visualize morphological behavior. The treated-water was analyzed for ERN by the spectroscopy, scanning electron microscopy–energy-dispersive X-ray analysis mode (SEM–EDX), and inductively coupled plasma–optical emission spectroscopy (ICP–OES) techniques. We studied factors (composition, size, viscosity, and time of exposure) affecting removal efficiency (%RE). The obtained green nanoemulsions (ENE1–ENE5) were stable and clear (<180 nm). ENE5 had the smallest size (58 nm), a low polydispersity index value (0.19), optimal viscosity (∼121.7 cP), and a high negative zeta potential value (−25.4 mV). A high %RE value (98.8%) was achieved with a reduced size, a high water amount, a low Capryol 90 content, and optimal viscosity as evidenced by the obtained results. Moreover, contact time had insignificant effect on %RE. UV–vis spectroscopy, SEM–EDX, and ICP–OES confirmed the absence of ERN from the treated water. Conclusively, ERN can easily be removed from polluted water employing green nanoemulsions prepared from the optimized excipients, and evaluated characteristics.

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Prediction of the pharmacokinetics and pharmacodynamics of topiroxostat in humans by integrating the physiologically based pharmacokinetic model with the drug-target residence time model

Cited by 19 publications

References 29 publications

Impact of Composition and Morphology of Ketoconazole-Loaded Solid Lipid Nanoparticles on Intestinal Permeation and Gastroplus-Based Prediction Studies

Impact of Composition and Morphology of Ketoconazole-Loaded Solid Lipid Nanoparticles on Intestinal Permeation and Gastroplus-Based Prediction Studies

Removal of azithromycin from aqueous bulk solution using water/ethanol/transcutol/capryol-90 green nanoemulsion

Green Nanoemulsion Water/Ethanol/Transcutol/LabM-Based Treatment of Pharmaceutical Antibiotic Erythromycin-Contaminated Aqueous Bulk Solution

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