Food & Function
·
2018
·Vol. 9
·期 11
·5880-5890
·
IF 3.289
Xiuling Tang,Huanhuan Zhao,Wei Jiang,Song Zhang,Shun Guo,Xiaobo Gao,Peng Yang,Lei Shi,Linna Liu
Dry citrus peel (Chenpi) is not only consumed as a dietary supplement, but also used for the treatment of respiratory diseases. Pinelliae Rhizoma Praeparatum (Banxia) is always used with Chenpi for the treatment of respiratory diseases, but β-sitosterol, the main active component in Banxia, as a food additive, shows no respiratory system activity. In the present study, the pharmacokinetic characters showed that the absorption of the active components of Chenpi was accelerated under pathological conditions combined with Banxia. Although the bioavailability of active components did not significantly change, the distribution of active components in tissues increased, particularly in the target organ. These results are consistent with the combination of Chenpi with β-sitosterol. Furthermore, the pharmacodynamics result also indicated that Chenpi combined with Banxia or β-sitosterol was able to ameliorate histopathologic damage and decrease the levels of inflammatory factors. The results suggest that pharmacokinetic interactions improve the pharmacological activity of Chenpi in respiratory diseases.
研究领域:
药理学
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中药学
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产品关联
DOI
PubMed
高影响因子
BMC Veterinary Research
·
2021
·Vol. 17
·期 1
·1-13
·
IF 2.741
Liu Xuesong,Yang Qingwen,Fan Yuying,Du Yuanyi,Lei Lei,Wang Dong,Liu Yun
Background Enrofloxacin is an antibacterial drug with broad-spectrum activity that is widely indicated for veterinary use. We aim to develop the clinical applications of Enrofloxacin against colibacillosis by using the neutropenic mice thigh infection model. Results The minimum inhibitory concentration (MIC) distribution of 67 isolated E. coli strains to ENR was calculated using CLSI guidelines. Whereas, the MIC 50 value calculation was considered as the population PD parameter for ENR against E. coli strains. The MIC values of 15 E. coli strains were found to be nearest to the MIC 50 i.e. , 0.25 μg/mL. Of all the tested strains, the PK-PD and E. coli disease model was established via selected E. coli strain i.e. , Heilong 15. We analyzed the PK characteristics of ENR and its metabolite ciprofloxacin (CIP) following a single subcutaneous (s.c.) injection of ENR (1.25, 2.5, 5, 10 mg/kg). The concentration-time profiling of ENR within the plasma specimens was determined by considering the non-compartmental analysis (NCA). The basic PK parameters of ENR for the peak drug concentration (C max ) and the area under the concentration-time curve (AUC) values were found to be in the range of 0.27–1.97 μg/mL and 0.62–3.14 μg.h/mL, respectively. Multiple s.c. injection over 24 h (1.25, 2.5, 5, 10 mg/kg at various time points i.e. , 6, 8, 12, and 24 h respectively) were administered to assess the targeted PD values. The Akaike Information Criterion (AIC) was used to choose PD models, and the model with the lowest AIC was chosen. The inhibitory E max model was employed to calculate the related PK-PD parameters. The results of our study indicated that there was a strong correlation between the AUC/MIC and various antibacterial activities (R 2 = 0.9928). The target values of dividing AUC/MIC by 24 h for bacteriostatic action were 1-log10 reduction, 2-log10 reduction, and 3-log10 reduction 0.325, 0.4375, 0.63, and 0.95 accordingly. Conclusion The identified pharmacodynamics targets for various antibacterial effects will be crucial in enhancing ENR clinical applications and serving as a key step in reducing bacterial resistance.
研究领域:
兽医学
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微生物学
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药理学
✓ 已验证
DOI
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-13
·
IF 15.7
Yang Jian,Gong Xia,Zheng Ying,Duan Hong,Chen Shuijin,Wu Tong,Yi Changqing,Jiang Lelun,Haick Hossam
Precision and personalized medicine for disease management necessitates real-time, continuous monitoring of biomarkers and therapeutic drugs to adjust treatment regimens based on individual patient responses. This study introduces a wearable Microneedle-based Continuous Biomarker/Drug Monitoring (MCBM) system, designed for the simultaneous, in vivo pharmacokinetic and pharmacodynamic evaluation for diabetes. Utilizing a dual-sensor microneedle and a layer-by-layer nanoenzyme immobilization strategy, the MCBM system achieves high sensitivity and specificity in measuring glucose and metformin concentrations in skin interstitial fluid (ISF). Seamless integration with a smartphone application enables real-time data analysis and feedback, fostering a pharmacologically informed approach to diabetes management. The MCBM system’s validation and in vivo trials demonstrate its precise monitoring of glucose and metformin, offering a tool for personalized treatment adjustments. Its proven biocompatibility and safety suit long-term usage. This system advances personalized diabetes care, highlighting the move towards wearables that adjust drug dosages in real-time, enhancing precision and personalized medicine.
研究领域:
生物医学工程
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药理学
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内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Veterinary Sciences
·
2025
·Vol. 12
·期 4
·294
·
IF 2.3
Tiantian Gao,Xuesong Liu,Di Qiu,Yanan Li,Zongsheng Qiu,Jingjing Qi,Shuxin Li,Xiaoyan Guo,Yan Zhang,Ziqi Wang,Xiang Gao,Yuhui Ma,Tianwen Ma
Simple SummaryBacterial infection is a major cause of death in foals.Escherichia coli(E. coli) is a Gram-negative bacterium that causes sepsis, which can be life-threatening in horses. Cefquinome has broad-spectrum antimicrobial activity and is widely used in the treatment of animal diseases. At the same time, it is the fourth generation of cephalosporin antibiotics for veterinary use, and it has good antibacterial activity against both Gram-positive and Gram-negative bacteria. Cefquinome is utilized for the treatment of septicemia induced byE. coli, as well as respiratory infections caused byStreptococcus equisubsp.zooepidemicusin foals. However, there is a lack of studies using cefquinome to targetE. colias a pathogen of sepsis. Pharmacokinetic/pharmacodynamic (PK/PD) modeling is a fundamental step in semi-mechanical methodology aimed at improving dose planning of systemically active antimicrobial agents. PK/PD models can determine the relationship between drug concentration, antibacterial action, and time, deriving the most effective dosing regimen. This study was based on this model to verify the optimal dosing regimen forE. coliinfection in foals and to provide a theoretical basis for the precision treatment of foals.Cefquinome is used to treat septicemia caused byEscherichia coli(E. coli) and respiratory infections caused byStreptococcus equisubsp.zooepidemicusin foals. However, studies reporting the use of cefquinome to targetE. colias pathogens of sepsis are lacking. Therefore, this study aimed to determine the optimal dosage regimen for cefquinome againstE. coliusing a PK/PD model. After the administration of 1 mg/kg cefquinome (intramuscularly or intravenously), blood samples were collected at different time points to determine the serum concentration of cefquinome via HPLC. The pharmacokinetic parameters were evaluated via NCA (WinNonlin 5.2.1 software). The main pharmacokinetic parameters of cefquinome in foals were as follows: after intravenous administration, the elimination half-life (T1/2β) was 2.35 h, the area under the curve (AUC0–last) was 12.33 μg·h/mL, the mean residence time (MRT0–last) was 2.67 h, and the clearance rate (CL) was 0.09 L/h/kg. After intramuscular administration, the peak concentration (Cmax) was 0.89 μg/mL, the time to reach the maximum serum concentration (Tmax) was 2.16 h, T1/2βwas 4.16 h, AUC0–lastwas 5.41 μg·h/mL, MRT0–lastwas 4.92 h, CL was 0.15 L/h/kg, and the absolute bioavailability (F) was 43.86%. An inhibitory sigmoid Emax model was used to integrate the PK/PD indices with ex vivo antimicrobial effects to identify pharmacodynamic targets (PDTs). According to the dose calculation formula, the doses of intramuscularly administered cefquinome required to achieve bacteriostatic effects, bactericidal effects, and bactericidal elimination were 1.10, 1.66, and 2.28 mg/kg, respectively. However, further studies are warranted to verify the therapeutic efficacy of cefquinome in clinical settings.
研究领域:
兽医学
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微生物学
·
药物动力学
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产品关联
DOI
PubMed
高影响因子
XENOBIOTICA
·
2019
·
IF 1.902
Huanying Ye,Danjuan Sui,Wei Liu,Yuannan Yuan,Zhen Ouyang,Yuan Wei
1. CYP2C11 is the most abundant isoform of cytochrome P450s (CYPs) in male rats and is considered the main enzyme for warfarin metabolism.2. To further access the in vivo function of CYP2C11 in warfarin metabolism and efficacy, a CYP2C11-null rat model was used to study warfarin metabolism with both in vitro and in vivo approaches. Prothrombin time (PT) of warfarin was also determined.3. The maximum rate of metabolism (Vmax) and intrinsic clearance (CLint) of liver microsomes from CYP2C11-null males were reduced by 37 and 64%, respectively, compared to those in Sprague Dawley (S-D) rats. The Km of liver microsomes from CYP2C11-null males was increased by 73% compared to that of S-D rats. The time to reach the maximum plasma concentration (Tmax) of warfarin in CYP2C11-null males was significantly delayed compared to that in S-D males, and the CL rate was also reduced. The PT of CYP2C11-null rats was moderately longer than that of S-D rats.4. In conclusion, the clearance rate of warfarin was mildly decreased and its anticoagulant effect was moderately increased in male rats following CYP2C11 gene knockout. CYP2C11 played a certain role in the clearance and efficacy of warfarin, while it did not seem to be essential.
研究领域:
药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 14
·4657
·
IF 4.927
Mengxin Cao,Jiawei Zuo,Jian-Guo Yang,Chenyao Wu,Yongan Yang,Wenjian Tang,Lili Zhu
To understand that 18β-Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetinic acid (GA) in rat plasma and tissues after oral administration of GAMG or GL. This analytical method was validated by linearity, LLOQ, specificity, recovery rate, matrix effect, etc. After oral administration, GAMG exhibited excellentCmax(2377.57 ng/mL),Tmax(5 min) and AUC0-T(6625.54 mg/L*h), which was much higher than theCmax(346.03 ng/mL),Tmax(2.00 h) and AUC0-T(459.32 mg/L*h) of GL. Moreover, GAMG had wider and higher tissue distribution in the kidney, spleen, live, lung, brain, etc. These results indicated that oral GAMG can be rapidly and efficiently absorbed and be widely distributed in tissues to exert stronger and multiple pharmacological activities. This provided a physiological basis for guiding the pharmacodynamic study and clinical applications of GAMG.Keywords:GAMG;glycyrrhetic acid;glycyrrhizin;pharmacokinetics;pharmacodynamics;tissue distribution
研究领域:
药理学
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中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
XENOBIOTICA
·
2021
·
IF 1.908
Xian-Mei Song,Bing-Jie Li,Yan-Yan Zhang,Wen-Jing Ge,She-Feng Zhang,Wei-Feng Cui,Geng-Sheng Li,Rui-Feng Liang
Diabetes mellitus is a chronic metabolic disorder with multiple complications, patients who receive metformin may have a simultaneous intake of herbal medicine containing rutaecarpine due to cardiovascular protection and hypolipidemic effects of rutaecarpine. There might be drug interactions between metformin and rutaecarpine. This study aimed to investigate the effects of rutaecarpine on the pharmacodynamics and pharmacokinetics of metformin in diabetic rats.The diabetic rat model was induced with high-fat diet and low dose streptozotocin. Metformin with or without rutaecarpine was administered by oral gavage for 42 days. Pharmacodynamics and pharmacokinetics parameters were evaluated.The pharmacodynamics results revealed that co-administration of rutaecarpine with metformin resulted in a remarkable reduction of serum glucose and lipid profiles in diabetic rats compared to metformin treated alone. The pharmacokinetics results showed that co-treatments of rutaecarpine with metformin did not affect the systemic exposure and renal distribution of metformin, but increased metformin concentration in liver. Furthermore, rutaecarpine increased Oct1-mediated metformin uptake into hepatocytes by upregulation of Oct1 expression in the liver.The above data indicate that rutaecarpine enhanced the anti-diabetic effect of metformin, which may be associated with the increased hepatic distribution of metformin through up-regulation of Oct1 in response to rutaecarpine.
研究领域:
药理学
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内分泌学
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糖尿病研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS
·
2018
·Vol. 41
·期 5
·706-718
·
IF 1.441
L. Zhang,Y. Li,Y. Wang,A. Sajid,S. Ahmed,X. Li
The aims of this study were to establish optimal doses of doxycycline (dox) against Haemophilus parasuis on the basis of pharmacokinetic–pharmacodynamic (PK-PD) integration modeling. The infected model was established by intranasal inoculation of organism in pigs and confirmed by clinical signs, blood biochemistry, and microscopic examinations. The recommended dose (20 mg/kg b.w.) was administered in pigs through intramuscular routes for PK studies. The area under the concentration 0- to 24-hr curve (AUC 0–24 ), elimination half-life ( T ½ke ), and mean residence time (MRT) of dox in healthy and H. parasuis -infected pigs were 55.51 ± 5.72 versus 57.10 ± 4.89 μg·hr/ml, 8.28 ± 0.91 versus 9.80 ± 2.38 hr, and 8.43 ± 0.27 versus 8.79 ± 0.18 hr, respectively. The minimal inhibitory concentration (MIC) of dox against 40 H. parasuis isolates was conducted through broth microdilution method, the corresponding MIC 50 and MIC 90 were 0.25 and 1 μg/ml, respectively. The Ex vivo growth inhibition data suggested that dox exhibited a concentration-dependent killing mechanism. Based on the observed AUC 24 hr /MIC values by modeling PK-PD data in H. parasuis -infected pigs, the doses predicted to obtain bacteriostatic, bactericidal, and elimination effects for H. parasuis over 24 hr were 5.25, 8.55, and 10.37 mg/kg for the 50% target attainment rate (TAR), and 7.26, 13.82, and 18.17 mg/kg for 90% TAR, respectively. This study provided a more optimized alternative for clinical use and demonstrated that the dosage 20 mg/kg of dox by intramuscular administration could have an effective bactericidal activity against H. parasuis .
研究领域:
兽医学
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微生物学
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药理学
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Dong Jiang,Huajin Tan,Rujiao Zhang,Kaikang Wang,Yujia Zhang,Xiaochuan Tan,Wensheng Zheng
Background Pediatric pulmonary arterial hypertension (PPAH) is a malignant progressive rare disease characterized by restricted pulmonary artery blood flow and progressively increasing blood pressure, which has shorter survival time of only about 10 months as compared to adults. Previous studies have shown that low-dose vardenafil hydrochloride (Var) could significantly improve the symptoms of PPAH. However, Var is currently available only in tablet form in the market for erectile dysfunction , and no special preparation is available for PPAH. Methods In this study, borneol-mediated vardenafil hydrochloride patch (BO-VarP) with sodium polyacrylate as the skeleton material was prepared by coating method, which was characterized by temperature resistance, formability, adhesive force, skin irritation and in vitro permeation. Blood concentration of optimized BO-VarP was measured by LC-MS/MS using intragastric administration (i.g.) as a control, and pharmacodynamic studies were conducted using a rat model of pulmonary arterial hypertension induced by monocrotaline . Results and discussion Optimized BO-VarP showed good appearance, with optimal temperature resistance and formability, appropriate adhesive force and low skin irritation, and its cumulative permeation flux was 14.9 times higher than patch without penetration enhancer . The blood concentration within therapeutic window of BO-VarP lasted longer than i.g., and BO-VarP could improve symptoms of PPAH by reducing pulmonary arterial pressure and right heart hypertrophy index. Conclusion BO-VarP had good therapeutic effect in PPAH rats and suitable compliance in children, which provided a potential industrial transdermal delivery system for the treatment of PPAH.
研究领域:
药理学
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儿科医学
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药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2023
·
IF 4.6
Boyu Fang,Shasha Jin,Wandi Du,Weimin Cai
Background Recent studies have reported a higher risk of bleeding among patients that are co-administrated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) and anticoagulant, which raises our concern about the possible TKIs-warfarin pharmacokinetic and pharmacodynamic interaction that could be life-threatening to tumor patients who take warfarin for preventing deep vein thrombosis (DVT). Methods Influences of anlotinib and fruquintinib on the pharmacokinetic and dynamic behavior of warfarin were estimated. Influence on the activity of cytochrome P450 (CYP450) enzymes was detected in vitro through rat liver microsomes. Quantitative analysis of blood concentration in rats was finished by a validated UHPLC-MS/MS method. Furthermore, pharmacodynamic interactions were studied in rats by monitoring prothrombin time (PT) and activated partial thromboplastin time (APTT), while Inferior vena cava (IVC) stenosis-induced DVT model was built to further investigate the antithrombotic effect after co-administration. Results Anlotinib inhibited the activity of cyp2c6, cyp3a1/2 and cyp1a2 in rat liver microsomes in a dose-dependent manner, meanwhile enhanced the AUC 0∼t and AUC 0∼∞ of R-warfarin. However, fruquintinib showed no effects on pharmacokinetics of warfarin. Anlotinib and fruquintinib co-administrated with warfarin was found to exert more significant increase on PT and APTT values than that taking warfarin alone. In IVC stenosis-induced DVT model rats, the co-administration groups significantly reduced the length of thrombus compared with the single warfarin group. Conclusions Anlotinib and fruquintinib enhanced the anticoagulated and antithrombotic effect of warfarin. The anlotinib-induced interaction may due to the inhibition of the metabolism of warfarin. The mechanism of the pharmacodynamic interaction between fruquintinib and warfarin should be further investigated.
研究领域:
肿瘤学
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药理学
·
血液学
✓ 已验证
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
·
2019
·
IF 3.532
Chao Liu,Nabil Farah,Wei Weng,Baixin Jiao,Meiyue Shen,Liang Fang
Permeation enhancer strategy is used to develop Benzoylaconitine (BA) of high molecular weight (603.7 Da) into transdermal patch . The present study was to achieve a patch with good analgesic and anti-inflammatory effects and investigate the relationship between physicochemical parameters of enhancers and enhancement strength. In vitro skin permeation study was used to evaluate the effect of enhancers, and correlation study was conducted to clarify the relationship between physicochemical parameters of enhancer and permeation amount. The enhancement molecular mechanism was characterized using FT-IR and molecular modeling. Finally, pharmacodynamic effect of BA patch was evaluated with analgesic and anti-inflammatory assessment. The correlation analysis indicated that the optimized patch containing permeation enhancer Plurol® Oleique CC497 with high surface tension (43.0 dyne/m), demonstrated the strongest skin permeation amount of 5.50 ± 0.21 μg/cm 2 . According to the FT-IR and molecular modeling study, the enhancer with high surface tension demonstrated maximum interaction strength ( E mix = −9.20 kcal/mol) with skin lipid and affected the skin protein region, which strongly disturbed skin lipid arrangement according to the results of ATR-FTIR study (wavenumber variation of ν as CH2 of skin lipid > 2.00 cm −1 ) and molecular modeling (Cohesive Energy Density of skin lipid bilayer = 1.04E + 08 kcal/mol). It was indicated that only based on sufficient interaction strength and disturbing of both lipophilic and hydrophilic area of stratum corneum, permeation enhancer was able to demonstrated great permeation enhancement effect. Finally, BA transdermal patch was developed and showed excellent analgesic and anti-inflammatory effect, which was a potential preparation for the treatment of inflammatory pain .
研究领域:
药理学
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药物递送系统
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生物医学工程
✓ 已验证
DOI
高影响因子
PULMONARY PHARMACOLOGY & THERAPEUTICS
·
2019
·
IF 2.669
Xiaojie Zhu,Ying Kong,Qi Liu,Yayuan Lu,Han Xing,Xiaoyu Lu,Yue Yang,Jiaqiu Xu,Ning Li,Di Zhao,Xijing Chen,Yang Lu
Pulmonary delivery of anti-cancer drugs in the form of nanoparticulate dry powders is considered a promising modality for treating lung cancer. However, it is not known whether the pharmacodynamics and pharmacokinetics of nano-preparations are altered after co-spray drying. In this study, we compared the physicochemical property, anti-cancer activity, tumor targeting and pharmacokinetic behavior of docetaxel-loaded folic acid-conjugated liposomes (LPs-DTX-FA) with those of dry powder prepared by co-spray-drying LPs-DTX-FA. The particle size and PDI after re-dispersion of the powder were increased. The re-dispersed liposomes showed increased cellular uptake via micropinocytosis and exhibited higher cytotoxicity than LPs-DTX-FA. Tumor targeting of re-dispersed liposomes was less effective compared with LPs-DTX-FA but the metabolism of re-dispersed liposomes was decreased. Tracheal administration resulted in a 45-fold higher concentration of docetaxel in the lung of Sprague Dawley rats at 30 min as compared with intravenous administration . Our results indicated that co-spray drying did change the properties, while tracheal administration of the dry powder provided higher drug exposure at the tumor site without increasing the exposure of other organs. Thus, inhaled dry powders might be clinically effective for treatment of lung cancer .
研究领域:
药理学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）