Widely distributed in plants,ent-kaurane diterpenoids could reduce the incidence of inflammatory.The most important active ingredient of Isodon serra(Maxim.)Hara is ent-kaurane diterpenoids,which contribute to the ant...Widely distributed in plants,ent-kaurane diterpenoids could reduce the incidence of inflammatory.The most important active ingredient of Isodon serra(Maxim.)Hara is ent-kaurane diterpenoids,which contribute to the anti-inflammatory pharmacological effects of Isodon serra.However,the ingredients,the active compounds,drug targets,inflammatory targets and exact molecular mechanism of Isodon serra in treating inflammatory are still unclear.The purpose of this study was to use the method of network pharmacological analysis to find the active compounds in Isodon serra.These active compounds match the library of ent-kaurane diterpenoids compounds we established,and we find all the eligible ent-kaurane diterpenoids compounds.Isodon serra related and anti-inflammatory targets were found and then combined to get intersection,which represented potential anti-inflammatory targets of active compounds in Isodon serra.Moreover,anti-inflammatory targets and active compounds targets protein-protein interaction network were merged to get the protein-protein interaction network intersection and core genes in anti-inflammatory target protein-protein interaction network.For the anti-inflammatory targets of Isodon serra,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were executed to confirm gene functions of Isodon serra in antagonizing inflammation.Finally,TCMSP analysis identified 10 active compounds out of 48 ent-kaurane.The pathway analysis showed enrichment for different pathways like AGE-RAGE signaling pathway in diabetic complications,small cell lung cancer and human cytomegalovirus infection,which were all connected to inflammatory.On the whole,the proposed method clearly identified the ent-kaurane diterpenoids of Isodon serra and the results gave the active compounds of Isodon serra for the first time.The combining use of the qualitative analysis of traditional Chinese medicine(TCM)and network pharmacological methods could discover potential drug targets and reveal the biological process of TCM,which would open up a new approach in the study of TCM in future.展开更多
In the present study,we optimized the ceftriaxone dosing regimens based on pharmacokinetic/pharmacodynamic(PK/PD)principles using Monte Carlo simulation(MCS).Based on PK/PD theory,MCS was performed using Crystal Ball ...In the present study,we optimized the ceftriaxone dosing regimens based on pharmacokinetic/pharmacodynamic(PK/PD)principles using Monte Carlo simulation(MCS).Based on PK/PD theory,MCS was performed using Crystal Ball software combining PK and PD parameters with 10000 simulation runs to calculate the probability of target attainment(PTA)and cumulative fraction of response(CFR)for the seven clinically common dosing regimens of ceftriaxone(1 g qd,1.5 g qd,1 g bid,2 g qd,1 g tid,1.5 g bid,and 2 g bid).A%fT≥50 as the target value expected to achieve satisfactory clinical efficacy and a dosing regimen with an obtained CFR≥90%or the ability to achieve the highest PTA was used as a reasonable choice for empirical antimicrobial therapy,i.e.the clinically optimal regimen.All eight pathogenic bacteria had a CFR>90%when the dosing regimen was 2 g bid and 1 g tid,seven pathogenic bacteria had a CFR>90%when the dosing regimen was 1 g bid and 1.5 g bid,except for Pseudomonas aeruginosa,and all pathogenic bacteria had a CFR<90%when the dosing regimen was 1 g qd and 1.5 g qd.The dosing regimens of 2 g bid and 1 g tid were effective against all eight pathogenic bacteria infections,and 1 g bid and 1.5 g bid dosing regimens were effective against the other seven pathogenic bacteria except for Pseudomonas aeruginosa.展开更多
In the present study,we aimed to explore the timing of dosing with dapagliflozin(DAPA)in patients with hypovolemia and the role of the clinical pharmacist in pharmacological monitoring.The clinical pharmacist was invo...In the present study,we aimed to explore the timing of dosing with dapagliflozin(DAPA)in patients with hypovolemia and the role of the clinical pharmacist in pharmacological monitoring.The clinical pharmacist was involved in the dosing regimen of two patients with hypovolemia using DAPA and advising patients with insufficient blood volume to withhold the use of the drug.They reviewed the relevant literature to provide a theoretical basis for clinicians and the role of clinical pharmacists in pharmacy services.When considering patients with hypovolemia,the clinical pharmacist can promptly identify that DAPA can reduce blood volume and provide rational advice and rationale for the patient‟s medication that is adopted by the clinician,resulting in an individualized dosing regimen for the patient.Clinical pharmacists are advised to pay attention to the dosing adjustments of DAPA when patients are in hypovolemia and to be more alert to the adverse effects that can result from its use.展开更多
The total ginsenosides of ginseng fruit are the main constituents of Zhenyuan capsule,which is mainly used for the treatment of cardiovascular diseases.It has been reported that ginsenoside can affect the activity of ...The total ginsenosides of ginseng fruit are the main constituents of Zhenyuan capsule,which is mainly used for the treatment of cardiovascular diseases.It has been reported that ginsenoside can affect the activity of CYP450 enzymes.Zhenyuan capsule and simvastatin may interact with each other through CYP3 A4 mediation,then affect the efficacy and even produce adverse reactions.However,no studies have investigated the effects of Zhenyuan capsule on the pharmacokinetics of simvastatin and its active metabolites.In this study,liquid chromatography–electrospray ionization–mass spectrometry(LC-MS/MS)was used to detect the pharmacokinetics of simvastatin and its active metabolites-simvastatin acid with or without Zhenyuan capsule in rats.Compared with the simvastatin alone,the pharmacokinetic parameters of simvastatin and simvastatin acid were significantly different in AUC0–24 and AUC0–∞,and they were decreased in varying degrees(P<0.05).It appeared that the Zhenyuan capsule might increase the activity of CYP3 A4 to some extent.展开更多
The purpose of this study was to establish a method for determining the free concentration of ceftriaxone based on hollow fiber centrifugal ultrafiltration(HFCF-UF)technology in combination with high-performance liqui...The purpose of this study was to establish a method for determining the free concentration of ceftriaxone based on hollow fiber centrifugal ultrafiltration(HFCF-UF)technology in combination with high-performance liquid chromatography(HPLC)for free pharmacokinetic studies and the prediction of ceftriaxone concentrations in lung tissue.This method only required centrifugation for a short time,and the filtrate could be injected directly for HPLC analysis without further treatment.The specificity,linearity,precision and stability of this method were validated for quantification of free ceftriaxone.Under the optimized conditions,the absolute recoveries were more than 92.5%.The intraday and interday precision RSDs were less than 3.6%.Additionally,nonspecific adsorption(NSB)between the analyte and the ultrafiltration membrane was considered.This method was successfully applied to the analysis of the free ceftriaxone concentration in rat plasma and lung tissue.The free ceftriaxone concentration of lung tissue could be predicted by using the linear formula Cfl=Cfp(0.342 x–0.0129)(x:time).This method also provides a reliable alternative for accurate monitoring of the free ceftriaxone concentration in therapeutic drug monitoring(TDM).展开更多
基金Hebei Administration of Traditional Chinese Medicine(Grant No.2021133)the Natural Science Foundation of Hebei Province of China(Grant No.H2019206562)the Key Projects of Hebei Education Department(Grant No.ZD2017244)。
文摘Widely distributed in plants,ent-kaurane diterpenoids could reduce the incidence of inflammatory.The most important active ingredient of Isodon serra(Maxim.)Hara is ent-kaurane diterpenoids,which contribute to the anti-inflammatory pharmacological effects of Isodon serra.However,the ingredients,the active compounds,drug targets,inflammatory targets and exact molecular mechanism of Isodon serra in treating inflammatory are still unclear.The purpose of this study was to use the method of network pharmacological analysis to find the active compounds in Isodon serra.These active compounds match the library of ent-kaurane diterpenoids compounds we established,and we find all the eligible ent-kaurane diterpenoids compounds.Isodon serra related and anti-inflammatory targets were found and then combined to get intersection,which represented potential anti-inflammatory targets of active compounds in Isodon serra.Moreover,anti-inflammatory targets and active compounds targets protein-protein interaction network were merged to get the protein-protein interaction network intersection and core genes in anti-inflammatory target protein-protein interaction network.For the anti-inflammatory targets of Isodon serra,Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were executed to confirm gene functions of Isodon serra in antagonizing inflammation.Finally,TCMSP analysis identified 10 active compounds out of 48 ent-kaurane.The pathway analysis showed enrichment for different pathways like AGE-RAGE signaling pathway in diabetic complications,small cell lung cancer and human cytomegalovirus infection,which were all connected to inflammatory.On the whole,the proposed method clearly identified the ent-kaurane diterpenoids of Isodon serra and the results gave the active compounds of Isodon serra for the first time.The combining use of the qualitative analysis of traditional Chinese medicine(TCM)and network pharmacological methods could discover potential drug targets and reveal the biological process of TCM,which would open up a new approach in the study of TCM in future.
基金2019 Second Hospital of Hebei Medical University Pro ject(Grant No.2h2019042)。
文摘In the present study,we optimized the ceftriaxone dosing regimens based on pharmacokinetic/pharmacodynamic(PK/PD)principles using Monte Carlo simulation(MCS).Based on PK/PD theory,MCS was performed using Crystal Ball software combining PK and PD parameters with 10000 simulation runs to calculate the probability of target attainment(PTA)and cumulative fraction of response(CFR)for the seven clinically common dosing regimens of ceftriaxone(1 g qd,1.5 g qd,1 g bid,2 g qd,1 g tid,1.5 g bid,and 2 g bid).A%fT≥50 as the target value expected to achieve satisfactory clinical efficacy and a dosing regimen with an obtained CFR≥90%or the ability to achieve the highest PTA was used as a reasonable choice for empirical antimicrobial therapy,i.e.the clinically optimal regimen.All eight pathogenic bacteria had a CFR>90%when the dosing regimen was 2 g bid and 1 g tid,seven pathogenic bacteria had a CFR>90%when the dosing regimen was 1 g bid and 1.5 g bid,except for Pseudomonas aeruginosa,and all pathogenic bacteria had a CFR<90%when the dosing regimen was 1 g qd and 1.5 g qd.The dosing regimens of 2 g bid and 1 g tid were effective against all eight pathogenic bacteria infections,and 1 g bid and 1.5 g bid dosing regimens were effective against the other seven pathogenic bacteria except for Pseudomonas aeruginosa.
文摘In the present study,we aimed to explore the timing of dosing with dapagliflozin(DAPA)in patients with hypovolemia and the role of the clinical pharmacist in pharmacological monitoring.The clinical pharmacist was involved in the dosing regimen of two patients with hypovolemia using DAPA and advising patients with insufficient blood volume to withhold the use of the drug.They reviewed the relevant literature to provide a theoretical basis for clinicians and the role of clinical pharmacists in pharmacy services.When considering patients with hypovolemia,the clinical pharmacist can promptly identify that DAPA can reduce blood volume and provide rational advice and rationale for the patient‟s medication that is adopted by the clinician,resulting in an individualized dosing regimen for the patient.Clinical pharmacists are advised to pay attention to the dosing adjustments of DAPA when patients are in hypovolemia and to be more alert to the adverse effects that can result from its use.
基金Research Fund Project of health and Family Planning Commission of Hebei Province(Grant No.20170571)。
文摘The total ginsenosides of ginseng fruit are the main constituents of Zhenyuan capsule,which is mainly used for the treatment of cardiovascular diseases.It has been reported that ginsenoside can affect the activity of CYP450 enzymes.Zhenyuan capsule and simvastatin may interact with each other through CYP3 A4 mediation,then affect the efficacy and even produce adverse reactions.However,no studies have investigated the effects of Zhenyuan capsule on the pharmacokinetics of simvastatin and its active metabolites.In this study,liquid chromatography–electrospray ionization–mass spectrometry(LC-MS/MS)was used to detect the pharmacokinetics of simvastatin and its active metabolites-simvastatin acid with or without Zhenyuan capsule in rats.Compared with the simvastatin alone,the pharmacokinetic parameters of simvastatin and simvastatin acid were significantly different in AUC0–24 and AUC0–∞,and they were decreased in varying degrees(P<0.05).It appeared that the Zhenyuan capsule might increase the activity of CYP3 A4 to some extent.
文摘The purpose of this study was to establish a method for determining the free concentration of ceftriaxone based on hollow fiber centrifugal ultrafiltration(HFCF-UF)technology in combination with high-performance liquid chromatography(HPLC)for free pharmacokinetic studies and the prediction of ceftriaxone concentrations in lung tissue.This method only required centrifugation for a short time,and the filtrate could be injected directly for HPLC analysis without further treatment.The specificity,linearity,precision and stability of this method were validated for quantification of free ceftriaxone.Under the optimized conditions,the absolute recoveries were more than 92.5%.The intraday and interday precision RSDs were less than 3.6%.Additionally,nonspecific adsorption(NSB)between the analyte and the ultrafiltration membrane was considered.This method was successfully applied to the analysis of the free ceftriaxone concentration in rat plasma and lung tissue.The free ceftriaxone concentration of lung tissue could be predicted by using the linear formula Cfl=Cfp(0.342 x–0.0129)(x:time).This method also provides a reliable alternative for accurate monitoring of the free ceftriaxone concentration in therapeutic drug monitoring(TDM).
