OBJECTIVE Danshen injection and Honghua injection,traditional Chinese medicine(TCM)injections,made from the extracts of Salvia miltiorrhiza Bge.and Carthamus tinctorius L.,have a potential to be developed into the use...OBJECTIVE Danshen injection and Honghua injection,traditional Chinese medicine(TCM)injections,made from the extracts of Salvia miltiorrhiza Bge.and Carthamus tinctorius L.,have a potential to be developed into the useful drugs for the.As the common TCM injections,Danshen injection is often combined with Honghua injection to treat cardiovascular disease.The purpose of this study was to investigate the pharmacokinetic parameters of Honghua injection combined with Danshen injection when they were coadministered intravenously in human and rats through the tail vein.METHODS Single and multiple doses of Danshen injection to study Danshen injection on Honghua injection pharmacokinetics parameters and single and multiple doses of Honghua injection to study Honghua injection on Danshen injection pharmacokinetics parameters.The plasma concentrations of hydroxysafflor A(HSYA)and tanshinol and salvianolic acid B were determined by the reliable high-performance liquid chromatography(HPLC)method.The concentrations of HSYA in urine of rats and human were also determined by HPLC method.DAS 2.1.1software was adopted for calculating the pharmacokinetic parameters.RESULTS The simultaneous intravenous Honghua injection and salvia miltiorrhiza injiection significantly altered the pharmacokinetic parameters of both injections when compared with the individual intravenous administration of each injection.The area under the concentration-timecurve(AUC)and maximum plasma concentration(Cmax)of HSYA and tanshinol and salvianolic acid B were significantly increased.The cumulative urine excretion of HSYA in human and rats during 24 h was decreased after two drugs were administered simultaneously by the intravenous.CONCLUSION Honghua injection and Danshen injection interact with each other following simultaneous intravenous and they have a synergistic action.This experiment has identified the pharmacokinetic parameters and provided a rationale for the clinical use of the drug combination.展开更多
During pre-clinical pharmacokinetic research, it is not easy to gather complete pharmacokinetic data in each animal. In some cases, an animal can only provide a single observation. Under this circumstance, it is not c...During pre-clinical pharmacokinetic research, it is not easy to gather complete pharmacokinetic data in each animal. In some cases, an animal can only provide a single observation. Under this circumstance, it is not clear how to utilize this data to estimate the pharmacokinetic parameters effectively. This study was aimed at comparing a new method to handle such single-observation-per-animal type data with the conventional method in estimating pharmacokinetic parameters. We assumed there were 15 animals within the study receiving a single dose by intravenous injection. Each animal provided one observation point. There were five time points in total, and each time point contained three measurements. The data were simulated with a one-compartment model with first-order elimination. The inter-individual variabilities （ⅡV） were set to 10%, 30% and 50% for both clearance （CL） and apparent volume of distribution （V）. A proportional model was used to describe the residual error, which was also set to 10%, 30% and 50%. Two methods （conventional method and the finite msampling method） to handle with the simulated single-observation-per-animal type data in estimating pharmacokinetic parameters were compared. The conventional method （MI） estimated pharmacokinetic parameters directly with original data, i.e., single-observation-per-animal type data. The finite resampling method （M2） was to expand original data to a new dataset by resampling original data with all kinds of combinations by time. After resampling, each individual in the new dataset contained complete pharmacokinetic data, i.e., in this study, there were 243 （C3^1×C3^1×C3^1×C3^1×C3^1） kinds of possible combinations and each of them was a virtual animal. The study was simulated 100 times by the NONMEM software. According to the results, parameter estimates of CL and V by M2 based on the simulated dataset were closer to their true values, though there was a small difference among different combinations of ⅡVs and the residual errors. In general, M2 was less advantageous over M1 when the residual error increased. It was also influenced by the levels of ⅡV as higher levels of IIV could lead to a decrease in the advantage of M2. However, M2 had no ability to estimate the ⅡV of parameters, nor did M1. The finite resampling method could provide more reliable results compared to the conventional method in estimating pharmacokinetic parameters with single-observation-per-animal type data. Compared to the inter-individual variability, the results of estimation were mainly influenced by the residual error.展开更多
The purpose of this study was to compare pharmacokinetic(PK)parameters obtained using two newly developed assays,HPLC-UV and UPLC-ESI-MS/MS.Selection of assay and results obtained therefrom are very important in PK st...The purpose of this study was to compare pharmacokinetic(PK)parameters obtained using two newly developed assays,HPLC-UV and UPLC-ESI-MS/MS.Selection of assay and results obtained therefrom are very important in PK studies and can have a major impact on the PK-based clinical dose and usage settings.For this study,we developed two new methods that are most commonly used in biosample analysis and focused on PK parameters obtained from them.By HPLC-UV equipped with a Luna-C8 column using UV detector,cefprozil diastereomers were separated using water containing 2%(V/V)acetic acid and acetonitrile as a mobile phase.By UPLC-ESI-MS/MS equipped with a HALO-C18 column,cefprozil diastereomers were separated using 0.5%(V/V)aqueous formic acid containing 5 mM ammoniumformate buffer and methanol as a mobile phase.Chromatograms showed high resolution,sensitivity,and selectivity without interference by plasma constituents.Both intra-and inter-day precisions(CV,%)were within 8.88%for HPLC-UV and UPLC-ESI-MS/MS.Accuracy of both methods was 95.67%-107.50%.These two analytical methods satisfied the criteria of international guidance and could be successfully applied to PK study.Comparison of PK parameters between two assays confirmed that there is a difference in the predicted minimum plasma concentrations at steady state,which may affect clinical dose and usage settings.Furthermore,we confirmed possible correlation between PK parameters and various biochemical parameters after oral administration of 1000 mg cefprozil to humans.展开更多
Higher alcohols are key factors affecting sensory quality and post-drinking comfort of alcoholic beverages.A strategy combining solid-phase extraction and gas chromatography-mass spectrometry(SPE-GC-MS)was established...Higher alcohols are key factors affecting sensory quality and post-drinking comfort of alcoholic beverages.A strategy combining solid-phase extraction and gas chromatography-mass spectrometry(SPE-GC-MS)was established to analyze the metabolism pattern of higher alcohols in rat plasma after gavage of 4 common alcoholic beverages including huangjiu,baijiu,wine and brandy.7 mL of dichloromethane was determined as the optimal extraction condition,and 8 higher alcohols were precisely quantified with detection limits of 1.82−11.65μg/L,recoveries of 89.07%−110.89%and fine repeatability.The fastest absorption and elimination rates of plasma total higher alcohols were observed in baijiu and huangjiu group,respectively,and the highest peak concentration was found in brandy group.Additionally,the metabolic rate of plasma isoamyl alcohol in huangjiu group was faster than that in wine group at the same intragastric administration dosage.This study may provide potential insight for evaluation of alcoholic beverage quality.展开更多
The resistance to antibacterials therapy has been increasing in recent years,^1,2 The rational use ofanti-bacterials should include： （1） choosing the right drugs according to the scope of their antibacterials funct...The resistance to antibacterials therapy has been increasing in recent years,^1,2 The rational use ofanti-bacterials should include： （1） choosing the right drugs according to the scope of their antibacterials function and making sure they are suitable for treatment of the microorganisms that have induced the infection;^3 （2） administering anti-bacterials by a rational method according to their pharmacodynamics;^4 （3） paying attention to the systemic condition of the patients according to pharmacokinetics of the drugs.^5,6展开更多
基金The project supported by 2016-2018 Anhui University Research Platform Innovation Team
文摘OBJECTIVE Danshen injection and Honghua injection,traditional Chinese medicine(TCM)injections,made from the extracts of Salvia miltiorrhiza Bge.and Carthamus tinctorius L.,have a potential to be developed into the useful drugs for the.As the common TCM injections,Danshen injection is often combined with Honghua injection to treat cardiovascular disease.The purpose of this study was to investigate the pharmacokinetic parameters of Honghua injection combined with Danshen injection when they were coadministered intravenously in human and rats through the tail vein.METHODS Single and multiple doses of Danshen injection to study Danshen injection on Honghua injection pharmacokinetics parameters and single and multiple doses of Honghua injection to study Honghua injection on Danshen injection pharmacokinetics parameters.The plasma concentrations of hydroxysafflor A(HSYA)and tanshinol and salvianolic acid B were determined by the reliable high-performance liquid chromatography(HPLC)method.The concentrations of HSYA in urine of rats and human were also determined by HPLC method.DAS 2.1.1software was adopted for calculating the pharmacokinetic parameters.RESULTS The simultaneous intravenous Honghua injection and salvia miltiorrhiza injiection significantly altered the pharmacokinetic parameters of both injections when compared with the individual intravenous administration of each injection.The area under the concentration-timecurve(AUC)and maximum plasma concentration(Cmax)of HSYA and tanshinol and salvianolic acid B were significantly increased.The cumulative urine excretion of HSYA in human and rats during 24 h was decreased after two drugs were administered simultaneously by the intravenous.CONCLUSION Honghua injection and Danshen injection interact with each other following simultaneous intravenous and they have a synergistic action.This experiment has identified the pharmacokinetic parameters and provided a rationale for the clinical use of the drug combination.
文摘During pre-clinical pharmacokinetic research, it is not easy to gather complete pharmacokinetic data in each animal. In some cases, an animal can only provide a single observation. Under this circumstance, it is not clear how to utilize this data to estimate the pharmacokinetic parameters effectively. This study was aimed at comparing a new method to handle such single-observation-per-animal type data with the conventional method in estimating pharmacokinetic parameters. We assumed there were 15 animals within the study receiving a single dose by intravenous injection. Each animal provided one observation point. There were five time points in total, and each time point contained three measurements. The data were simulated with a one-compartment model with first-order elimination. The inter-individual variabilities （ⅡV） were set to 10%, 30% and 50% for both clearance （CL） and apparent volume of distribution （V）. A proportional model was used to describe the residual error, which was also set to 10%, 30% and 50%. Two methods （conventional method and the finite msampling method） to handle with the simulated single-observation-per-animal type data in estimating pharmacokinetic parameters were compared. The conventional method （MI） estimated pharmacokinetic parameters directly with original data, i.e., single-observation-per-animal type data. The finite resampling method （M2） was to expand original data to a new dataset by resampling original data with all kinds of combinations by time. After resampling, each individual in the new dataset contained complete pharmacokinetic data, i.e., in this study, there were 243 （C3^1×C3^1×C3^1×C3^1×C3^1） kinds of possible combinations and each of them was a virtual animal. The study was simulated 100 times by the NONMEM software. According to the results, parameter estimates of CL and V by M2 based on the simulated dataset were closer to their true values, though there was a small difference among different combinations of ⅡVs and the residual errors. In general, M2 was less advantageous over M1 when the residual error increased. It was also influenced by the levels of ⅡV as higher levels of IIV could lead to a decrease in the advantage of M2. However, M2 had no ability to estimate the ⅡV of parameters, nor did M1. The finite resampling method could provide more reliable results compared to the conventional method in estimating pharmacokinetic parameters with single-observation-per-animal type data. Compared to the inter-individual variability, the results of estimation were mainly influenced by the residual error.
文摘The purpose of this study was to compare pharmacokinetic(PK)parameters obtained using two newly developed assays,HPLC-UV and UPLC-ESI-MS/MS.Selection of assay and results obtained therefrom are very important in PK studies and can have a major impact on the PK-based clinical dose and usage settings.For this study,we developed two new methods that are most commonly used in biosample analysis and focused on PK parameters obtained from them.By HPLC-UV equipped with a Luna-C8 column using UV detector,cefprozil diastereomers were separated using water containing 2%(V/V)acetic acid and acetonitrile as a mobile phase.By UPLC-ESI-MS/MS equipped with a HALO-C18 column,cefprozil diastereomers were separated using 0.5%(V/V)aqueous formic acid containing 5 mM ammoniumformate buffer and methanol as a mobile phase.Chromatograms showed high resolution,sensitivity,and selectivity without interference by plasma constituents.Both intra-and inter-day precisions(CV,%)were within 8.88%for HPLC-UV and UPLC-ESI-MS/MS.Accuracy of both methods was 95.67%-107.50%.These two analytical methods satisfied the criteria of international guidance and could be successfully applied to PK study.Comparison of PK parameters between two assays confirmed that there is a difference in the predicted minimum plasma concentrations at steady state,which may affect clinical dose and usage settings.Furthermore,we confirmed possible correlation between PK parameters and various biochemical parameters after oral administration of 1000 mg cefprozil to humans.
基金supported by the National Natural Science Foundation of China(22138004 and 32001828).
文摘Higher alcohols are key factors affecting sensory quality and post-drinking comfort of alcoholic beverages.A strategy combining solid-phase extraction and gas chromatography-mass spectrometry(SPE-GC-MS)was established to analyze the metabolism pattern of higher alcohols in rat plasma after gavage of 4 common alcoholic beverages including huangjiu,baijiu,wine and brandy.7 mL of dichloromethane was determined as the optimal extraction condition,and 8 higher alcohols were precisely quantified with detection limits of 1.82−11.65μg/L,recoveries of 89.07%−110.89%and fine repeatability.The fastest absorption and elimination rates of plasma total higher alcohols were observed in baijiu and huangjiu group,respectively,and the highest peak concentration was found in brandy group.Additionally,the metabolic rate of plasma isoamyl alcohol in huangjiu group was faster than that in wine group at the same intragastric administration dosage.This study may provide potential insight for evaluation of alcoholic beverage quality.
文摘The resistance to antibacterials therapy has been increasing in recent years,^1,2 The rational use ofanti-bacterials should include： （1） choosing the right drugs according to the scope of their antibacterials function and making sure they are suitable for treatment of the microorganisms that have induced the infection;^3 （2） administering anti-bacterials by a rational method according to their pharmacodynamics;^4 （3） paying attention to the systemic condition of the patients according to pharmacokinetics of the drugs.^5,6
