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Quantitative assessment of the relevance of organic-aniontransporting-polypeptide 1B1 and 2B1 polymorphisms in fexofenadine pharmacokinetic variants via pharmacometrics

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Journal of Pharmaceutical Analysis 2023年第6期13卷 660-672页

作者： Ji-Hun Jang Seung-Hyun Jeong Yong-Bok Lee department of pharmacy College of PharmacyChonnam National UniversityGwangju61186Republic of Korea department of pharmacy College of PharmacySunchon National UniversitySuncheon-si57922Republic of Korea

Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmacokinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic variability.Polymorphisms of the organic-anion-transporting-polypeptide(OATP)1B1 and 2B1 have been proposed to be closely related to fexofenadine pharmacokinetic diversity.Therefore,modeling was performed using fexofenadine oral exposure data according to the OATP1B1-and 2B1-polymorphisms.OATP1B1 and 2B1 were identified as effective covariates of clearance(CL/F)and distribution volume(V/F)-CL/F,respectively,in fexofenadine pharmacokinetic variability.CL/F and average steady-state plasma concentration of fexofenadine differed by up to 2.17-and 2.20-folds,respectively,depending on the OATP1B1 polymorphism.Among the individuals with different OATP2B1 polymorphisms,the CL/F and V/F differed by up to 1.73-and 2.00-folds,respectively.Ratio of the areas under the curves following single-and multiple-administrations,and the cumulative ratio were significantly different between OATP1B1-and 2B1-polymorphism groups.Based on quantitative prediction comparison through a model-based approach,OATP1B1 was confirmed to be relatively more important than 2B1 regarding the degree of effect on fexofenadine pharmacokinetic variability.Based on the established pharmacokineticpharmacodynamic relationship,the difference in fexofenadine efficacy according to genetic polymorphisms of OATP1B1 and 2B1 was 1.25-and 0.87-times,respectively,and genetic consideration of OATP1B1 was expected to be important in the pharmacodynamics area as well.This population pharmacometrics study will be a very useful starting point for fexofenadine precision medicine.

关键词： OATP1B1 OATP2B1 Fexofenadine Population pharmacometrics Genetic polymorphism

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Use of stimulatory responsive soft nanoparticles for intracellular drug delivery

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Nano Research 2023年第5期16卷 6974-6990页

作者： Krystal A Hughes Bishal Misra Maryam Maghareh Sharan Bobbala department of Pharmaceutical Sciences West Virginia University School of PharmacyMorgantownWV 26505USA department of Clinical pharmacy West Virginia University School of PharmacyMorgantownWV 26505USA

Drug delivery has made tremendous advances in the last decade.Targeted therapies are increasingly common,with intracellular delivery highly impactful and sought after.Intracellular drug delivery systems have limitations due to imprecise and non-targeted release profiles.One way this can be addressed is through using stimuli-responsive soft nanoparticles,which contain materials with an organic backbone such as lipids and polymers.The choice of biomaterial is essential for soft nanoparticles to be responsive to internal or external stimuli.The nanoparticle must retain its integrity and payload in non-targeted physiological conditions while responding to particular intracellular environments where payload release is desired.Multiple internal and external factors could stimulate the intracellular release of drugs from nanoparticles.Internal stimuli include pH,oxidation,enzymes,while external stimuli include ultrasound,light,electricity,magnetic fields.Stimulatory responsive soft nanoparticulate systems specifically utilized to modulate intracellular delivery of drugs are explored in this review.

关键词： nanoparticles biomaterials stimuli-responsive targeted delivery intracellular drug delivery

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Pharmacological insights into Chukrasia velutina bark:Experimental and computer-aided approaches

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Animal Models and Experimental Medicine 2022年第4期5卷 377-388页

作者： Israt Jahan Shahenur Alam Sakib Najmul Alam Mohuya Majumder Sanjida Sharmin A.S.M.Ali Reza department of pharmacy International Islamic University ChittagongChittagongBangladesh department of pharmacy East West UniversityDhakaBangladesh

Background:Chukrasia velutina is an enthnomedicinally used plant reported to have significant medicinal values.The present study aimed to explore the pharmacological activities of bark methanol extract using in vitro,in vivo and in silico models.Methods:The study was designed to investigate the pharmacological effects of methanol extract of Chukrasia velutina bark(MECVB)through in vitro,in vivo and in silico assays.Analgesic activity was tested using formalin-i nduced nociception and acetic acid-i nduced writhing assays while the antipyretic effect was tested using yeast-i nduced hyperthermia in mice model.The antioxidant effect was tested using the DPPH and reducing power assay and the cytotoxic screening was tested using the brine shrimp lethality bioassay.In addition,in silico studies were conducted using computer aided methods.Results:In the acetic acid-i nduced writhing assay,the extract showed 28.36%and 56.16%inhibition of writhing for doses of 200 and 400 mg/kg,respectively.Moreover,a dose-dependent formalin-i nduced licking response was observed in both early and late phase.In yeast-i nduced pyrexia,the MECVB exhibited(p<0.05)antipyretic effect.The extract demonstrated an ICvalue of 78.86μg/ml compared with ascorbic acid(IC23.53μg/ml)in the DPPH scavenging assay.The compounds sitosterol,5,7-dimethoxycoumarin and scopoletin were seen be effective in molecular docking scores against COX-I(2OYE),COX-II(6COX)and human peroxiredoxin 5(1HD2).In ADME/T analysis,5,7-dimethoxycoumarin and scopoletin satisfied Lipinski’s rule of five and thus are potential drug candidates.Conclusion:The bark of Chukrasia velutina showed significant analgesic and antipyretic properties and is a potential source of natural anti-oxidative agents.

关键词： anti-nociceptive antioxidant antipyretic Chukrasia velutina cytotoxicity

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Is Regular Probiotic Practice Safe for Management of Sepsis?

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Chinese Journal of Integrative Medicine 2022年第2期28卷 185-192页

作者： Rishabh Kumar Alok Shiomurti Tripathi Nidhi Sharma Gaaminepreet Singh Lucy Mohapatra department of Pharmacology ISF College of PharmacyMoga(Punjab)India department of Pharmacology Amity Institute of PharmacyAmity UniversityLucknow(UP)India

For decades,the gut has been thought to play an important role in sepsis pathogenesis.Sepsis is a serious life-threatening,chronic condition of an infection caused by dysregulated host immune response in most of the intensive care unit patients.Probiotics have dual roles in polymicrobial sepsis i.***.probiotics may induce sepsis in many cases and may prevent its prognosis in many cases.Experimental evidence from both pre-clinical and clinical studies have demonstrated that probiotic therapy ameliorates various inflammatory mediators such as tumor necrosis factor,interleukin-10(IL-10),IL-6,etc.,in septicemia.In addition,probiotic use was also found to reduce the severity of pathological conditions associated with irritable bowel disorder and prevent development of endocarditis in septicemia.On contrary,probiotic therapy in neonatal and athymic adult mice fail to provide any beneficial effects on mortality and sepsis-induced inflammation.Importantly,in few clinical trials probiotic use was found to aggravate sepsis by promoting inflammatory cascade rather than suppressing it.This review discusses various studies regarding the beneficial or harmful effects associated with probiotic therapy in sepsis.

关键词： sepsis probiotics microbial flora immune system

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Determinants of survival outcomes among esophageal cancer patients at a national referral hospital in Kenya

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Chronic Diseases and Translational Medicine 2023年第1期9卷 20-28页

作者： Amsalu Degu Peter N.Karimi Sylvia A.Opanga David G.Nyamu department of Pharmaceutics and pharmacy Practice School of Pharmacy and Health SciencesUnited States International University–AfricaNairobiKenya department of pharmacy Faculty of Health SciencesUniversity of NairobiNairobiKenya

Introduction:The overall 5-year survival rate for esophageal cancer patients in low-and middle-income countries was reported to be low,despite the availability of advanced treatments.Thus,this study aimed to assess determinants of survival outcomes among esophageal cancer patients in Kenya.Methods:A retrospective cohort study was employed among 299 adult esophageal cancer patients.The data were collected using a data abstraction tool consisting of patients’clinical characteristics and survival outcome measuring parameters.Statistical Package for the Social Sciences(SPSS)statistical software(version 20.0,IBM.USA)was used to analyze the data.The Kaplan–Meier and Cox regression analyses were used to determine the survival outcome and determinants of mortality,respectively.Results:The mortality rate was 43.1%,and 11.1%of patients demonstrated distant metastases in the follow-up period.Despite treatment,20.1%had progressed disease,and 13.0%did not respond to treatment.Radiotherapy(AHR:3.3,95%CI:1.4−7.8,p=0.007),chemotherapy(AHR:3.9,95%CI:1.2−6.1,p=0.020),and chemoradiation(AHR:5.6,95%CI:1.6−10.2,p=0.006)were the significant determinants of survival in advanced stage(III and and IV)patients.Conclusions:There was a high mortality rate,disease progression,and nonresponse of esophageal cancer patients.Hence,it is essential to improve the survival of patients through early detection and timely initiation of the available treatment options.

关键词： determinants esophageal cancer mortality survival outcomes

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Houttuynia cordata polysaccharide alleviated intestinal injury and modulated intestinal microbiota in H1N1 virus infected mice

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Chinese Journal of Natural Medicines 2019年第3期17卷 187-197页

作者： CHEN Mei-Yu LI Hong LU Xiao-Xiao LING Li-Jun WENG Hong-Bo SUN Wei CHEN Dao-Feng ZHANG Yun-Yi department of Pharmacology School of Pharmacy Fudan University department of Pharmacognosy School of Pharmacy Fudan University

Houttuynia cordata polysaccharide(HCP) is extracted from Houttuynia cordata, a key traditional Chinese medicine. The study was to investigate the effects of HCP on intestinal barrier and microbiota in H1N1 virus infected mice. Mice were infected with H1N1 virus and orally administrated HCP at a dosage of 40 mg×kg^(–1)×d^(–1). H1N1 infection caused pulmonary and intestinal injury and gut microbiota imbalance. HCP significantly suppressed the expression of hypoxia inducible factor-1α and decreased mucosubstances in goblet cells, but restored the level of zonula occludens-1 in intestine. HCP also reversed the composition change of intestinal microbiota caused by H1N1 infection, with significantly reduced relative abundances of Vibrio and Bacillus, the pathogenic bacterial genera. Furthermore, HCP rebalanced the gut microbiota and restored the intestinal homeostasis to some degree. The inhibition of inflammation was associated with the reduced level of Toll-like receptors and interleukin-1β in intestine, as well as the increased production of interleukin-10. Oral administration of HCP alleviated lung injury and intestinal dysfunction caused by H1N1 infection. HCP may gain systemic treatment by local acting on intestine and microbiota. This study proved the high-value application of HCP.

关键词： HIN1 influenza virus Houttuynia cordata Inflammation Intestinal Barrier Microbiota Polysaccharide

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Development of a surface plasmon resonance biosensor for accurate and sensitive quantitation of small molecules in blood samples

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Journal of Pharmaceutical Analysis 2022年第6期12卷 929-936页

作者： Minyu Qi Diya Lv Ying Zhang Dongyao Wang Xiaofei Chen Zhenyu Zhu Zhanying Hong Yifeng Chai Hai Zhang Yan Cao department of Biochemical pharmacy Faculty of PharmacyNaval Medical UniversityShanghai200433China Pharmaceutical Analysis and Testing Center Faculty of PharmacyNaval Medical UniversityShanghai200433China department of Pharmaceutical Analysis Faculty of PharmacyNaval Medical UniversityShanghai200433China department of pharmacy Shanghai First Maternity and Infant HospitalTongji University School of MedicineShanghai201204China

Therapeutic drug monitoring(TDM)has played an important role in clinical medicine for precise dosing.Currently,chromatographic technology and immunoassay detection are widely used in TDM and have met most of the needs of clinical drug therapy.However,some problems still exist in practical applications,such as complicated operation and the influence of endogenous substances.Surface plasmon resonance(SPR)has been applied to detect the concentrations of small molecules,including pesticide residues in crops and antibiotics in milk,which indicates its potential for in vivo drug detection.In this study,a new SPR-based biosensor for detecting chloramphenicol(CAP)in blood samples was developed and validated using methodological verification,including precision,accuracy,matrix effect,and extraction recovery rate,and compared with the classic ultra-performance liquid chromatographyultraviolet(UPLC-UV)method.The detection range of SPR was 0.1-50 ng/mL and the limit of detection was 0.099±0.023 ng/mL,which was lower than that of UPLC-UV.The intra-day and inter-day accuracies of SPR were 98%-114% and 110%-122%,which met the analysis requirement.The results show that the SPR biosensor is identical to UPLC-UV in the detection of CAP in rat blood samples;moreover,the SPR biosensor has better sensitivity.Therefore,the present study shows that SPR technology can be used for the detection of small molecules in the blood samples and has the potential to become a method for therapeutic drug monitoring.

关键词： Surface plasmon resonance UPLC-UV Chloramphenicol Methodological verification

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Study on the dynamic variation of the secondary metabolites in Viscum coloratum using targeted metabolomics

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Chinese Journal of Natural Medicines 2023年第4期21卷 308-320页

作者： ZHANG Ruizhen DUAN Rong WANG Weiqing YU Zhiguo LI Yun ZHAO Yunli department of Pharmaceutical Analysis School of PharmacyShenyang Pharmaceutical UniversityShenyang 110016China department of pharmacy the Second Hospital of Dalian Medical UniversityDalian 116023China

Viscum coloratum(Kom.)Nakai is a well-known medicinal plant.However,the optimal harvest time for V.coloratum is unknown.Few studies were performed to analyze compound variation during storage and to improve post-harvest quality control.Our study aimed to comprehensively evaluate the quality of V.coloratum in different growth stages,and determine the dynamic variation of metabolites.Ultra-performance liquid chromatography tandem mass spectrometry was used to quantify 29 compounds in V.coloratum harvested in six growth periods,and the associated biosynthetic pathways were explored.The accumulation of different types of compounds were analyzed based on their synthesis pathways.Grey relational analysis was used to evaluate the quality of v.coloratum across different months.The compound variation during storage was analyzed by a high-temperature high-humidity accelerated test.The results showed that the quality of V.coloratum was the hightest in March,followed by November,and became the lowest in July.During storage,compounds in downstream steps of the biosynthesis pathway were first degraded to produce the upstream compounds and some low-molecular-weight organic acids,leading to an increase followed by a decrease in the content of some compounds,and resulted in a large gap during the degradation time course among different compounds.Due to the rapid rate and large degree of degradation,five compounds were tentatively designated as“early warning components”for quality control.This report provides reference for better understanding the biosynthesis and degradation of metabolites in V.coloratum and lays a theoretical foundation for rational application of V.coloratum and better quality control of V.coloratum during storage.

关键词： Viscum coloratum Harvesting period Storage Plant metabolomics Quality control

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Capillary electrophoresis methods for impurity profiling of drugs:A review of the past decade

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Journal of Pharmaceutical Analysis 2022年第1期12卷 15-28页

作者： Mansi Shah Nrupesh Patel Nagja Tripathi Vivek K.Vyas department of Pharmaceutical Analysis Institute of PharmacyNirma UniversityAhmedabad382481GujaratIndia department of Pharmacognosy Institute of PharmacyNirma UniversityAhmedabad382481GujaratIndia department of Pharmaceutical Chemistry Institute of PharmacyNirma UniversityAhmedabad382481GujaratIndia

Capillary electrophoresis(CE)is widely used for the impurity profiling of drugs that contain stereochemical centers in their structures,analysis of biomolecules,and characterization of biopharmaceuticals.Currently,CE is the method of choice for the analysis of foodstuffs and the determination of adulterants.This article discusses the general theory and instrumentation of CE as well as the classification of various CE techniques.It also presents an overview of research on the applications of different CE techniques in the impurity profiling of drugs in the past decade.The review briefly presents a comparison between CE and liquid chromatography methods and highlights the strengths of CE using drug compounds as examples.This review will help scientists,fellow researchers,and students to understand the applications of CE techniques in the impurity profiling of drugs.

关键词： Capillary electrophoresis Impurities Impurity profiling Drugs

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Anti-aging properties of Ribes fasciculatum in Caenorhabditis elegans

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Chinese Journal of Natural Medicines 2016年第5期14卷 335-342页

作者： Hoon Jeon Dong Seok Cha department of Oriental pharmacy College of Pharmacy Woosuk University

The present study investigated the effects and underlying mechanism of ethylacetate fraction of Ribes fasciculatum(ERF) on the lifespan and stress tolerance using a Caenorhabditis elegans model. The longevity activity of ERF was determined by lifespan assay under normal culture condition. The survival rate of nematodes under various stress conditions was assessed to validate the effects of ERF on the stress tolerance. To determine the antioxidant potential of ERF, the superoxide dismutase(SOD) activities and intracellular reactive oxygen species(ROS) levels were investigated. The ERF-mediated change in SOD-3 expression was examined using GFP-expressing transgenic strain. The effects of ERF on the aging-related factors were investigated by reproduction assay and pharyngeal pumping assay. The intestinal lipofuscin levels of aged nematodes were also measured. The mechanistic studies were performed using selected mutant strains. Our results indicated that ERF showed potent lifespan extension effects on the wild-type nematode under both normal and various stress conditions. The ERF treatment also enhanced the activity and expression of superoxide dismutase(SOD) and attenuated the intracellular ROS levels. Moreover, ERF-fed nematodes showed decreased lipofuscin accumulation, indicating ERF might affect age-associated changes in C. elegans. The results of mechanistic studies indicated that there was no significant lifespan extension in ERF-treated daf-2, age-1, sir-2.1, and daf-16 null mutants, suggesting that they were involved in ERF-mediated lifespan regulation. In conclusion, R. fasciculatum confers increased longevity and stress resistance in C. elegans via SIR-2.1-mediated DAF-16 activation, dependent on the insulin/IGF signaling pathway.

关键词：秀丽隐杆线虫抗老化性能超氧化物歧化酶寿命试验应力条件绿色荧光蛋白 ERF 长寿命

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