THERAPEUTIC DRUG MONITORING
·
2015
·Vol. 37
·期 6
·776
·
IF 2.376
Zhang Zhi-qing,Dong Wei-chong,Yang Xiu-ling,Zhang Jin-feng,Jiang Xin-Hui,Jing Shao-jun,Yang Hong-le,Jiang Ye
Background: Free drug analysis is increasingly becoming popular in therapeutic drug monitoring (TDM). Centrifugal ultrafiltration (CF-UF) is the primary method to separate free drug from that of bound drug. However, the volume ratio of ultrafiltrate to sample solution ( V u / V s ) affects the accuracy of CF-UF, which highly depends on the different plasma conditions. Plasma protein concentrations in patients are different from those observed in healthy subjects, and there are also significant differences among patients with different diseases. Only very few studies have reported on the effect of protein concentration on the analysis methodology of free drug by CF-UF. Methods: In this study, valproic acid was used as the representative drug, and plasma samples with different albumin concentrations were analyzed by CF-UF and hollow fiber centrifugal ultrafiltration (HFCF-UF). Results: There was no significant difference of free drug concentrations by HFCF-UF and CF-UF when plasma albumin concentrations ranged 40–60 g/L. However, at low albumin concentrations (<40 g/L), a considerable difference was detected, and the difference was increased with the decrease of plasma albumin concentration. When the albumin concentration was as low as 10 g/L, the free drug concentration was 17.3 mcg/mL by CF-UF, whereas it was 10.2 mcg/mL by HFCF-UF. Conclusions: The accuracy of free drug measurement by CF-UF was albumin concentration dependent. However, such an effect was not observed when samples were prepared by HFCF-UF, which was more suitable for TDM of plasma samples from different patients. Therefore, this method could be readily applied to the measurement of free valproic acid plasma concentrations for TDM in patients.
研究领域:
药理学
·
临床医学
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DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHIC SCIENCE
·
2013
·Vol. 52
·期 10
·1173-1180
·
IF 0.794
Zhang Jin-Feng,Zhang Zhi-Qing,Dong Wei-Chong,Jiang Ye
A novel and sensitive high-performance liquid chromatographic (HPLC) method has been developed and validated for the determination of valproic acid (VPA) in human plasma. The method was based on derivatization of VPA using 2-bromo-2′-acetonaphthone as a new derivatization reagent. Caprylic acid was used as an internal standard (IS). Under the optimized extraction and derivatization conditions, the method showed good linearity in the range of 0.05–200 μg mL−1 and the limit of detection was as low as 0.01 μg mL−1. The relative standard deviation for intra-day and inter-day (n = 5) was <5%. The recovery ranged from 95.2 to 101.4%. The proposed method is proved to be highly sensitive, simple and rapid, and was successfully applied to the analysis of VPA in plasma samples from patients with generalized epilepsy.
研究领域:
分析化学
·
医学检验
·
药代动力学
✓ 已验证
DOI
PubMed
高影响因子
Pharmacogenomics & Personalized Medicine
·
2021
·
IF 3.912
Xikun Wu,Weichong Dong,Haoran Li,Xiuling Yang,Yiran Jin,Zhiqing Zhang,Ye Jiang
Purpose To perform therapeutic drug monitoring (TDM) of total and free plasma valproic acid (VPA) concentrations in pediatric patients with epilepsy and to analyze related factors.Patients and Methods Pediatric epileptic patients treated in 2015–2019 in our hospital were assessed. Total and free plasma VPA concentrations were obtained by UPLC and LC-MS/MS, respectively. Regression analysis was performed to examine the associations of free plasma VPA with total plasma VPA and plasma protein binding rate. The impacts of individual situation, CYP2C9 genotype, and drug combination on VPA concentration were examined.Results Of the 251 patients, 81 had lower total concentrations than effective therapeutic levels; 86 and 31 patients had infections and central nervous system dysplasia, respectively. VPA’s daily doses and free drug concentrations were significantly lower in the CYP2C9 *3/*3 genotype group versus the CYP2C9 *1/*3 and CYP2C9 *1/*1 groups (P<0.05). Free and total VPA concentrations were linked by Y = 0.0004 X2 + 0.042 X + 0.3035 (r=0.6981); VPA plasma protein binding rate and free VPA concentration were related by Y = 0.0003 X2 - 0.0127 X + 0.9777 (r=0.8136). Both total and free VPA concentrations were significantly decreased in patients simultaneously administered phenobarbital, meropenem and biapenem (P<0.05), with therapeutic failure after meropenem/biapenem co-administration.Conclusion Free VPA amounts have nonlinear relationships with total VPA amounts and plasma protein binding rate in epileptic children. Additionally, CYP2C9 *3/*3 expression affects VPA metabolism. Since phenobarbital affects VPA metabolism, TDM is recommended. Meanwhile, carbapenem-co-administration with VPA should be prohibited.
研究领域:
医学
·
药理学
·
遗传学
✓ 已验证
DOI
高影响因子
CNS Neuroscience & Therapeutics
·
2025
·Vol. 31
·期 7
·e70499
·
IF 5
Xinqi Fang,Junhan Wu,Yuan Hong,Jiexun Bu,Wenpeng Zhang,Zheng Ouyang,Wei Hua,Ying Mao
We present a novel point‐of‐care mass spectrometry system enabling rapid, real‐time quantification of valproic acid directly from whole blood. This bedside platform delivers serum‐equivalent results within 3 min and captures pharmacokinetic variability perioperatively, supporting individualized antiseizure therapy and timely clinical decision‐making in neurosurgical patients.
研究领域:
临床神经科学
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药物分析
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神经外科
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质谱技术
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个体化医疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2023
·Vol. 47
·期 35
·16675-16685
·
IF 3.3
Xiaoqian Jiang,Aihua Qu,Xinxin Xu,Hua Kuang,Liqiang Liu,Liguang Xu,Chuanlai Xu
Valproic acid (VPA) is mainly used in the clinic to treat epilepsy, for which the therapeutic window is narrow to avoid causing adverse reactions such as hepatotoxicity and teratogenicity. Therefore, timely therapeutic drug monitoring is needed. A hapten containing a benzene ring and an amino group was designed and used to screen a monoclonal antibody (mAb) 3G10 with high specificity and sensitivity. The IC50 value of mAb 3G10 was ascertained as 68.13 ng mL−1 through an indirect competitive enzyme-linked immunosorbent assay. A colloidal gold-based immunochromatographic strip (CG-ICS) for the detection of free VPA in human serum was developed with gold-labeled mAb 3G10. Qualitative analysis of human serum samples can be conducted through visual observation. The visual limit of detection (vLOD) was 2 μg mL−1, and the cut-off value was 100 μg mL−1. A standard curve for quantitative detection was generated using a portable scanner, with a calculated LOD (cLOD) value of 0.144 μg mL−1 and a linear range of 0.565–48.385 μg mL−1. Comparing the results of CG-ICS for actual positive samples with those of a direct chemiluminescence kit, there was a good correlation between the two methods. Therefore, our CG-ICS can be applied to the rapid clinical monitoring of free VPA.
研究领域:
医学诊断
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药理学
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Yuan Yuyang,Li Tianyu,Ye Zhichao,Feng Yuyao,Chen Zhe,Wang Yusen,Sun Yiqiao,Wu Haoyu,Yang Zhaodong,Wang Yifan,Zhang Yiran,Huang Liquan,Liang Bo
Bipolar disorder is a chronic mental disease with a heavy social and economic burden that causes extreme mood swings in patients. Valproate is a first-line drug for bipolar disorder patients to stabilize their daily mood. However, an excessive amount of valproate in the blood could induce severe adverse effects, which necessitates the monitoring of blood valproate levels for patients. Here, we developed an innovative electrochemical sensor for selective and simple detection of valproate based on a molecularly imprinted polymer membrane via one-step electropolymerization. Gold nanoparticles were electrochemically modified to the screen-printed electrode under the selective membrane to enhance its conductivity and stability. The successfully fabricated biosensor was characterized by scanning electron microscopy, cyclic voltammetry, and differential pulse voltammetry methods. The binding of the target molecules to the valproate-customized biomimetic polypyrrole membrane blocks cavities in the membrane and alters its electric properties, which can be detected as a decrease in the peak current by differential pulse voltammetry method. The peak current change presents a great log-linear response to the valproate concentration around the therapeutic window. The limit of detection of this method was 17.48 μM (LOD, S/N = 3) and the sensitivity was 31.86 μM μA−1. Furthermore, the biosensors exhibited both satisfying specificity with the interference of other psychological pharmaceutical drugs and uniformity among sensors, indicating their potential and reliability in translational application. This simple and reliable method of sensing valproate molecules primarily provides an exceptional solution to valproate point-of-care testing in clinical practice.
研究领域:
生物医学工程
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分析化学
·
药物监测
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2023
·
IF 5.6
Yan Li,Ke Li,Weihao Zhao,Haodong Wang,Xiaodong Xue,Xianghui Chen,Wantao Li,Peihao Xu,Kexin Wang,Pengfei Liu,Xuefei Tian,Rongguo Fu
Background: As a novel non-apoptotic cell death, ferroptosis has been reported to play a crucial role in acute kidney injury (AKI), especially cisplatin-induced AKI. Valproic acid (VPA), an inhibitor of histone deacetylase (HDAC) 1 and 2, is used as an antiepileptic drug. Consistent with our data, a few studies have demonstrated that VPA protects against kidney injury in several models, but the detailed mechanism remains unclear. Results: In this study, we found that VPA prevents against cisplatin-induced renal injury via regulating glutathione peroxidase 4 (GPX4) and inhibiting ferroptosis. Our results mainly indicated that ferroptosis presented in tubular epithelial cells of AKI humans and cisplatin-induced AKI mice. VPA or ferrostatin-1 (ferroptosis inhibitor, Fer-1) reduced cisplatin-induced AKI functionally and pathologically, which was characterized by reduced serum creatinine, blood urea nitrogen, and tissue damage in mice. Meanwhile, VPA or Fer-1 treatment in both in vivo and in vitro models, decreased cell death, lipid peroxidation, and expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), reversing downregulation of GPX4. In addition, our study in vitro indicated that GPX4 inhibition by siRNA significantly weakened the protective effect of VPA after cisplatin treatment. Conclusion: Ferroptosis plays an essential role in cisplatin-induced AKI and inhibiting ferroptosis through VPA to protect against renal injury is a viable treatment in cisplatin-induced AKI.
研究领域:
药理学
·
肾病学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Wentao Sun,Yue Gao,Yubing Wu,Wei Wu,Chaofan Wang,JiaXiao Chen,Changjiao Luan,Ming Hua,Weili Liu,Weijuan Gong,Xingjie Ma
Background Accumulation of senescent cells in tissues and their downstream effect programs have emerged as key drivers of aging and age-associated pathologies. Recent progresses in senotherapeutics indicated that either selectively killing senescent cells with senolytics or suppressing the senescence-associated secretory phenotype (SASP) secretion using senomorphics contributes to extending of the healthy lifespan and alleviating numerous age-related disorders in mice. Purpose However, the potential side-effects and long-term cytotoxicity of the above novel compounds have not yet been determined. Therefore, it seems to be more efficient to explore new senotherapeutical functions from approved drugs. Methods The effects of valproic acid (VPA), a derivative of valine, in cellular senescence were evaluated by senescence-associated β galactosidase (SA-β-Gal) staining, flow cytometry and western blot (WB). The cell viability was tested using CCK-8 kits. Cell apoptosis was detected by Annexin V-EGFP/PI apoptosis detection kit. Cell autophagy was checked using GFP-RFP-LC3 ratiometric plasmid. The roles of VPA in lung aging were investigated by in vivo experiments using H&E and Masson staining, WB, as well as electronic microscope strategies. Results Here we identified VPA was able to induce an over-accumulation of reactive oxygen species (ROS) (>1.5 times increasing) and apoptosis (>2 times increasing) of senescent cells. Mechanistically, VPA activated the phospholipid modifying enzyme membrane-bound O-acyltransferase domain-containing protein 1 (MBOAT1), which was repressed during senescence, then promoted mitochondrial autophagy and apoptosis. In addition, VPA was also found to alleviate therapy induced abnormal mitochondria and lung aging phenotype (>1.5 times decreasing of lung fibrosis markers and >2.5 times increasing of naïve/memory CD4+ or CD8+ cells) in vivo . Conclusion Taken together, our study demonstrated that VPA was able to selectively killing senescent cells both in vitro and in vivo , and thus shedding light on new functions and novel potential application of VPA in anti-aging and anti-age-associated diseases.
研究领域:
衰老
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药理学
·
细胞生物学
·
治疗学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Neuroinflammation
·
2024
·
IF 9.3
Kai Wang,Shufen Zhang,Yunxia Wang,Xiaomei Wu,Lijuan Wen,Tingting Meng,Xiangyu Jin,Sufen Li,Yiling Hong,Jia Ke,Yichong Xu,Hong Yuan,Fuqiang Hu
Background and purpose Neurodevelopmental disorders (NDDs) are characterized by abnormalities in brain development and neurobehaviors, including autism. The maternal–fetal interface (MFI) is a highly specialized tissue through which maternal factors affect fetal brain development. However, limited research exists on restoring and maintaining MFI homeostasis and its potential impact on NDDs. This study explores the role of placental indoleamine 2,3-dioxygenase (IDO-1) in MFI homeostasis and fetal brain development. Experimental Approach The maternal-fetal barrier was disrupted by sodium valproate (VPA) in pregnant mice, whose offspring show typical autism-like behaviors. Ultrastructural analysis and flow cytometric analysis were conducted to observe the morphological and immune system changes. Behavioral tests and immunofluorescence staining was used to investigate the ability and mechanism of taprenepag to alleviate the abnormal behaviors of VPA-exposed offspring and normalize the development of serotonergic neurons. Key results In VPA-exposed pregnant mice, the downregulation of IDO-1 led to maternal immune overactivation and disruption of maternal-fetal barrier, resulting in excessive 5-HT synthesis in the placenta. This process disrupted the development of the serotonergic neuronal system in the offspring, resulting in impaired development of serotonergic neurons, thalamocortical axons, and NDDs in the progeny. However, a single injection of taprenepag at E13.5 ultimately upregulated placental IDO-1 through amplifying the positive feedback loop COX-2/PGE 2 /PTGER-2/IDO-1 and abolished these alterations. Conclusion Taprenepag improved autism-like behaviors in the offspring of VPA-exposed mice by addressing placental IDO-1 downregulation. This study highlights the potential of targeting IDO-1 to mitigate MFI disruption and NDD development. Supplementary Information The online version contains supplementary material available at 10.1186/s12974-024-03300-7.
研究领域:
神经科学
·
免疫学
·
发育生物学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Progress in Biomaterials
·
2023
·Vol. 12
·期 2
·75-86
·
IF 4.9
Jafarimanesh Mohammad Amin,Ai Jafar,Shojaei Shahrokh,Khonakdar Hossein Ali,Darbemamieh Goldis,Shirian Sadegh
Hydrogels have been increasingly applied in tissue regeneration and drug delivery systems (DDS). In this study, the capacity of valproic acid (Val) encapsulated within hybrid of alginate (Alg)-chitosan (Cs) (Alg-Cs) hydrogel containing Cs nanoparticle (Npch) with/without human endometrial stem cells (hEnSC) was initially examined for regeneration of spinal cord injury (SCI). To evaluate the stability of the synthesized hydrogels zeta potential necessary measurements were made. Physicochemically, the developed hydrogels were evaluated using Fourier-transform infrared (FTIR) spectroscopy. The physical properties including degradation rate, swelling ability, and tunability of the synthesized hydrogels were studied. To evaluate the nerve regeneration ability of the synthesized hydrogels, 35 Sprague–Dawley rats were undergone SCI. The spinal cords were exposed using laminectomy in T9-T10 area and the hemi-section SCI model was made. The rats were then randomly divided into 5 groups ( n = 7) including, Alg-Cs/Npch, Alg-Cs/Npch/hEnSCs, Alg-Cs/Npch/Val, and Alg-Cs/Npch/hEnScs/Val, and the control groups without any intervention. The FTIR spectra showed band frequencies and assignments of Val, Alg-Cs, and alginate. Nanoparticles were formulated with a mean diameter of 187 and 210 nm, for Val/Alg-Cs and Alg-Cs, respectively. The loading of Val into Alg-Cs led to its reduced size by about 40 nm. The Cs-Npch/Val hydrogels degraded faster than the Alg-Cs-/Npch/Val hydrogel specifically in extended time of incubation. A higher swelling capacity of Alg-Cs/Npch hydrogel, compared to Cs/Npch/Val and Alg-Cs/Npch/Val hydrogels, was found. The Cs-Npch/Val hydrogels degraded faster than Alg-Cs-/Npch/Val hydrogel. The Alg-Cs/Npch/hEnSCs/Val could regenerate the damaged nerve fibers and histologically prevent the SCI-induced vacuolization spaces. The prepared Alg-Cs/Npch/Val could be a suitable polymeric carrier for taurine drugs as bioactive substrate in nerve tissue engineering (NTE) and DDS.
研究领域:
药理学
·
组织工程
·
神经科学
·
干细胞研究
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·
IF 3.4
Chongchong Liu,Jiangyan Sun,Xiaoming Shen,Shefang Li,Sha Luo,Na Chen,Yunke Zhang
Epilepsy is a chronic neurological disorder. Drug-resistant epilepsy (DRE) accounts for about one-third of epilepsy patients worldwide. Peimine, a main active component of Fritillaria, has been reported to show anti-inflammatory effects. However, its potential therapeutic role in DRE is not yet fully understood. In this work, a DRE rat model was established by injecting 1 μg kainic acid (KA), followed by a 250 mg/kg administration of valproic acid (VPA) from day 4–31. Rats were treated with different doses of peimine (2.5 mg/kg, 5 mg/kg and 10 mg/kg) daily from day 32–62. In vitro, BV-2 microglia were exposed to different doses of peimine (7.5 μg/ml, 15 μg/ml, and 30 μg/ml) in presence of LPS. The aim of this study was to investigate the potential therapeutic effects of peimine on DRE. The results showed that peimine efficiently suppressed the KA-induced epileptic behaviors of rats in a dose-dependent manner, as recorded by electroencephalography. Furthermore, peimine ameliorated hippocampal neuron injury in DRE rats, and promoted an M1-to-M2 microglial phenotype shift in a dose-dependent manner. Mechanistically, peimine inhibited the TLR4/NF-κB/HIF-1α signaling pathway both in vivo and in vitro. Additionally, peimine suppressed the apoptosis of primary neurons induced by LPS-treated microglia. In conclusion, peimine augments the microglial polarization towards an M2 phenotype by inhibiting the TLR4/NF-κB/HIF-1α signaling pathway, thereby attenuating DRE.
研究领域:
神经病学
·
药理学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Peixin Li,Yanfang Sun,Lei Nie,Amin Shavandi,Khaydar E. Yunusov,Yinjian Hua,Guohua Jiang
Androgenetic alopecia (AGA) is a transracial and cross-gender disease worldwide with a higher prevalence among young individuals. Traditional oral or subcutaneous injections are often used to treat AGA, however, they may cause severe side-effects and therefore effective treatments for AGA are currently lacking. In this work, to treat AGA, we developed a composite paste system based on minoxidil (MXD)-loaded nanoparticles and valproic acid (VPA) with the assistance of roller-microneedles (roller-MNs). The matrix of composite paste systems is carboxymethyl cellulose (CMC), hyaluronic acid (HA) and polyvinylpyrrolidone (PVP). The roller-MNs can create microchannels in the skin to enhance drug transdermal efficiency. With the combined effects of the stimulation hair follicle (HF) regrowth by upregulating Wnt/beta-catenin of VPA and the mechanical microchannels induced by roller-MNs, the as-prepared composite paste systems successfully boost perifollicular vascularization, and activate hair follicle stem cells, thereby inducing notably faster hair regeneration at a lower administration frequency on AGA mouse model compared with minoxidil. This approach offers several benefits, including the avoidance of efficacy loss due to the liver's first-pass effect associated with oral drug, reduction in the risk of infection from subcutaneous injection, and significant decrease in the side effects of lower-dose MXD.
研究领域:
药学
·
生物医学工程
·
皮肤科
·
纳米技术
·
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）