[目的]建立芍药内酯苷的药动学-药效学(PK-PD)模型。[方法]首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给予辛芍组方后的不同时间点所得血浆样本中芍药内酯苷的药物浓度,获得药时曲线;同时采用试剂盒测定不同时间点所得血浆样本中...[目的]建立芍药内酯苷的药动学-药效学(PK-PD)模型。[方法]首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给予辛芍组方后的不同时间点所得血浆样本中芍药内酯苷的药物浓度,获得药时曲线;同时采用试剂盒测定不同时间点所得血浆样本中的超氧化物歧化酶(SOD)和乳酸脱氢酶(LDH)含量,获得时效曲线。然后用Win Non Lin软件采用房室模型的分析方法对芍药内酯苷的药代动力学参数进行拟合,获得PK参数。在此基础之上,固定相关的药代动力学参数,对时效关系进行拟合,得到相关的PD参数,根据PD参数,建立辛芍组方中芍药内酯苷的PK-PD模型。[结果]当以SOD为药效指标时,可得辛芍组方中芍药内酯苷的PK-PD模型为E=21.04+(7.16×Ce)/(Ce+372.4);当以LDH为药效指标时,可得辛芍组方中代表成分芍药内酯苷的PK-PD模型为E=216.83-(37.31×Ce)/(Ce+0.04)。[结论]SOD和LDH的浓度与芍药内酯苷的浓度存在一定的相关性。芍药内酯苷可通过提高SOD、降低LDH发挥抗氧化作用来实现保护脑缺血再灌注损伤。展开更多
本研究旨在建立辛芍组方中灯盏甲素的PK-PD结合模型。首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给药后的不同时间点所得血浆样本中灯盏甲素的药物浓度,获得药时曲线;同时采用试剂盒测定不同时间点所得血浆样本中的两种药效指标(...本研究旨在建立辛芍组方中灯盏甲素的PK-PD结合模型。首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给药后的不同时间点所得血浆样本中灯盏甲素的药物浓度,获得药时曲线;同时采用试剂盒测定不同时间点所得血浆样本中的两种药效指标(SOD和LDH),获得时效曲线。然后用Win Non Lin软件采用房室模型的分析方法对灯盏甲素的药代动力学参数进行拟合,获得PK参数。在此基础之上,固定相关的药代动力学参数,对时效关系进行拟合,得到相关的PD参数,根据PD参数,建立辛芍组方中灯盏甲素的PK-PD结合模型。当以SOD为药效指标时,可得辛芍组方中灯盏甲素的PK-PD模型为E=20.67+(1.22×Ce)/(Ce+5.58);当以LDH为药效指标时,可得辛芍组方中代表成分灯盏甲素的PK-PD模型为E=214.17-(32.72×Ce)/(Ce+0.08)。结果表明,SOD和LDH的浓度与灯盏甲素的浓度存在一定的相关性。辛芍组方及其主要活性成分灯盏甲素可通过提高SOD、降低LDH发挥抗氧化作用来实现保护脑缺血再灌注损伤。展开更多
Doxycycline hydrochloride and florfenicol combination(DoxHcl&FF)is an effective treatment for respiratory diseases.In the study,our objective Was to evaluate the activity of DoxHcl&FF against Actinobacillus pl...Doxycycline hydrochloride and florfenicol combination(DoxHcl&FF)is an effective treatment for respiratory diseases.In the study,our objective Was to evaluate the activity of DoxHcl&FF against Actinobacillus pleuropneumoniae(APP)in porcine pulmonary epithelial lining fluid(PELF)and the optimal dosage scheme to avoid the development of resistance.The DoxHcl&FF Was administered intramuscularly(IM)at 20mg/kg,and the PELF was collected at differ-ent time points.The minimum inhibitory concentration(MIC)and time-mortality curves were also included in the study.Based on the sigmoid Emax equation and dose equations,the study integrated the in vivo pharmacokinetic data of infected pigs and ex vivo pharmacodynamic data to obtain the area under concentration time curve(AUCo-24h)MIC values in PELF and achieve bacteriostatic activity,bactericidal activity and the virtual eradication of bacteria.The study showed that the combination of DoxHcl and FF caused no significant changes in PK parameters.The peak concentration(Cmax)of FF in healthy and diseased pigs was 8.87±0.08 and 8.67±0.07μg/mL,the_AUCo-24h were.172.75±2.52 and 18022±3.13 h-μg/mL,the Cmax of DoxHcl was 7.91±0.09 and 7.99±0.05μg/mL,and the AUCo-24h was 129.96±3.70 h-μg/mL and 169.82±4.38 h-μg/mL.DoxHcl&FF showed strong concentra-tion-dependent tendencies.The bacteriostatic,bactericidal,and elimination activity were calculated as 5.61,18.83 and 32.68 h,and the doses were 1.37(bacteriostatic),4.59(bactericidal)and 7.99(elimination)mg/kg.These findings indicated that the calculated recommended dose could assist in achieving more precise administration,increasing the effectiveness of DoxHcl&FF treatment for APP infections.展开更多
文摘[目的]建立芍药内酯苷的药动学-药效学(PK-PD)模型。[方法]首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给予辛芍组方后的不同时间点所得血浆样本中芍药内酯苷的药物浓度,获得药时曲线;同时采用试剂盒测定不同时间点所得血浆样本中的超氧化物歧化酶(SOD)和乳酸脱氢酶(LDH)含量,获得时效曲线。然后用Win Non Lin软件采用房室模型的分析方法对芍药内酯苷的药代动力学参数进行拟合,获得PK参数。在此基础之上,固定相关的药代动力学参数,对时效关系进行拟合,得到相关的PD参数,根据PD参数,建立辛芍组方中芍药内酯苷的PK-PD模型。[结果]当以SOD为药效指标时,可得辛芍组方中芍药内酯苷的PK-PD模型为E=21.04+(7.16×Ce)/(Ce+372.4);当以LDH为药效指标时,可得辛芍组方中代表成分芍药内酯苷的PK-PD模型为E=216.83-(37.31×Ce)/(Ce+0.04)。[结论]SOD和LDH的浓度与芍药内酯苷的浓度存在一定的相关性。芍药内酯苷可通过提高SOD、降低LDH发挥抗氧化作用来实现保护脑缺血再灌注损伤。
文摘本研究旨在建立辛芍组方中灯盏甲素的PK-PD结合模型。首先采用液质联用法测定大鼠脑缺血再灌注损伤模型给药后的不同时间点所得血浆样本中灯盏甲素的药物浓度,获得药时曲线;同时采用试剂盒测定不同时间点所得血浆样本中的两种药效指标(SOD和LDH),获得时效曲线。然后用Win Non Lin软件采用房室模型的分析方法对灯盏甲素的药代动力学参数进行拟合,获得PK参数。在此基础之上,固定相关的药代动力学参数,对时效关系进行拟合,得到相关的PD参数,根据PD参数,建立辛芍组方中灯盏甲素的PK-PD结合模型。当以SOD为药效指标时,可得辛芍组方中灯盏甲素的PK-PD模型为E=20.67+(1.22×Ce)/(Ce+5.58);当以LDH为药效指标时,可得辛芍组方中代表成分灯盏甲素的PK-PD模型为E=214.17-(32.72×Ce)/(Ce+0.08)。结果表明,SOD和LDH的浓度与灯盏甲素的浓度存在一定的相关性。辛芍组方及其主要活性成分灯盏甲素可通过提高SOD、降低LDH发挥抗氧化作用来实现保护脑缺血再灌注损伤。
基金supported by the National Natural Science Foundation of China(32072920)the National Key Research and Development Program of China(2017YFD0501402)+1 种基金the Fundamental Research Funds for the Central Universities(2662022DKPY007)the HZAU-AGIS Cooperation Fund(SZYJY2022024).
文摘Doxycycline hydrochloride and florfenicol combination(DoxHcl&FF)is an effective treatment for respiratory diseases.In the study,our objective Was to evaluate the activity of DoxHcl&FF against Actinobacillus pleuropneumoniae(APP)in porcine pulmonary epithelial lining fluid(PELF)and the optimal dosage scheme to avoid the development of resistance.The DoxHcl&FF Was administered intramuscularly(IM)at 20mg/kg,and the PELF was collected at differ-ent time points.The minimum inhibitory concentration(MIC)and time-mortality curves were also included in the study.Based on the sigmoid Emax equation and dose equations,the study integrated the in vivo pharmacokinetic data of infected pigs and ex vivo pharmacodynamic data to obtain the area under concentration time curve(AUCo-24h)MIC values in PELF and achieve bacteriostatic activity,bactericidal activity and the virtual eradication of bacteria.The study showed that the combination of DoxHcl and FF caused no significant changes in PK parameters.The peak concentration(Cmax)of FF in healthy and diseased pigs was 8.87±0.08 and 8.67±0.07μg/mL,the_AUCo-24h were.172.75±2.52 and 18022±3.13 h-μg/mL,the Cmax of DoxHcl was 7.91±0.09 and 7.99±0.05μg/mL,and the AUCo-24h was 129.96±3.70 h-μg/mL and 169.82±4.38 h-μg/mL.DoxHcl&FF showed strong concentra-tion-dependent tendencies.The bacteriostatic,bactericidal,and elimination activity were calculated as 5.61,18.83 and 32.68 h,and the doses were 1.37(bacteriostatic),4.59(bactericidal)and 7.99(elimination)mg/kg.These findings indicated that the calculated recommended dose could assist in achieving more precise administration,increasing the effectiveness of DoxHcl&FF treatment for APP infections.
