Gabexate mesilate（GM） is a trypsin inhibitor,and mainly used for treatment of various acute pancreatitis,including traumatic pancreatitis（TP）,edematous pancreatitis,and acute necrotizing pancreatitis. However,due ...Gabexate mesilate（GM） is a trypsin inhibitor,and mainly used for treatment of various acute pancreatitis,including traumatic pancreatitis（TP）,edematous pancreatitis,and acute necrotizing pancreatitis. However,due to the characteristics of pharmacokinetics,the clinical application of GM still needs frequently intravenous administration to keep the blood drug concentration,which is difficult to manage. Specially,when the blood supply of pancreas is directly damaged,intravenous administration is difficult to exert the optimum therapy effect. To address it,a novel thermosensitive in-situ gel of gabexate mesilate（GMTI） was developed,and the optimum formulation of GMTI containing 20.6%（w/w） P-407 and 5.79%（w/w） P188 with different concentrations of GM was used as a gelling solvent. The effective drug concentration on trypsin inhibition was examined after treatment with different concentrations of GMTI in vitro,and GM served as a positive control. The security of GMTI was evaluated by hematoxylin-eosin（HE） staining,and its curative effect on grade Ⅱ pancreas injury was also evaluated by testing amylase（AMS）,C-reactive protein（CRP） and trypsinogen activation peptide（TAP）,and pathological analysis of the pancreas. The trypsin activity was slightly inhibited at 1.0 and 5.0 mg/m L in GM group and GMTI group,respectively（P〈0.05 vs. P-407）,and completely inhibited at 10.0 and 20.0 mg/m L（P〈0.01 vs. P-407）. After local injection of 10 mg/m L GMTI to rat leg muscular tissue,muscle fiber texture was normal,and there were no obvious red blood cells and infiltration of inflammatory cells. Furthermore,the expression of AMS,CRP and TAP was significantly increased in TP group as compared with control group（P〈0.01）,and significantly decreased in GM group as compared with TP group（P〈0.01）,and also slightly inhibited after 1.0 and 5.0 mg/m L GMTI treatment as compared with TP group（P〈0.05）,and significantly inhibited after 10.0 and 20.0 mg/m L GMTI treatment as compared展开更多
Aim: Firstly, to quantify active healthcare professional (HCP) time and costs associated with subcutaneous (SC) administration of trastuzumab (Herceptin?) compared with the standard intravenous infusion (IV) in the tr...Aim: Firstly, to quantify active healthcare professional (HCP) time and costs associated with subcutaneous (SC) administration of trastuzumab (Herceptin?) compared with the standard intravenous infusion (IV) in the treatment of patients with HER2-positive early breast cancer within the adjuvant PrefHer trial setting;secondly, to measure patient time in the care unit and patient infusion chair time for both routes of administration. Methods: A UK multi-centre prospective, observational Time and Motion study was conducted alongside the PrefHer trial (ClinicalTrials.gov id: NCT01401166). Trained observers measured the duration of each SC and IV related task that HCPs undertook and recorded patient time in the chemotherapy unit and infusion chair. The type and quantity of medical consumables used with each route of administration were also collected. Twenty-four patient episodes were recorded (12 SC, 12 IV). Mean total administration time was calculated as the mean sum of task times, both for IV and SC formulations. The mean cost of each route of administration was calculated as the mean cost of HCP time plus the mean cost of consumables used. HCP time was costed using Personal Social Services Research Unit. Consumables were costed using hospital pharmacy data and online sources. Results: Mean active HCP time for IV administration was 92.6 minutes compared with 24.6 minutes for SC administration. The mean cost for IV preparation and administration was ￡144.96 (￡132.05 of HCP time and ￡12.92 of consumables) versus ￡33.15 (￡31.99 of HCP time and ￡1.17 of consumables) for SC administration. Mean time spent in the care unit and in the infusion chair was 94.5 minutes and 75 minutes respectively for IV, and 30.3 minutes and 19.8 minutes for SC. SC administration of trastuzumab could translate to a time saving of 68 minutes (versus IV) with a total cost saving of ￡111.81 per patient episode. This equates to a potential saving of ￡2012.58 over a full course of adjuvant treatment (18 cycles). Conclusion: Subst展开更多
基金supported by National Natural Science Foundation of China(No.81471682 and 81327003)
文摘Gabexate mesilate（GM） is a trypsin inhibitor,and mainly used for treatment of various acute pancreatitis,including traumatic pancreatitis（TP）,edematous pancreatitis,and acute necrotizing pancreatitis. However,due to the characteristics of pharmacokinetics,the clinical application of GM still needs frequently intravenous administration to keep the blood drug concentration,which is difficult to manage. Specially,when the blood supply of pancreas is directly damaged,intravenous administration is difficult to exert the optimum therapy effect. To address it,a novel thermosensitive in-situ gel of gabexate mesilate（GMTI） was developed,and the optimum formulation of GMTI containing 20.6%（w/w） P-407 and 5.79%（w/w） P188 with different concentrations of GM was used as a gelling solvent. The effective drug concentration on trypsin inhibition was examined after treatment with different concentrations of GMTI in vitro,and GM served as a positive control. The security of GMTI was evaluated by hematoxylin-eosin（HE） staining,and its curative effect on grade Ⅱ pancreas injury was also evaluated by testing amylase（AMS）,C-reactive protein（CRP） and trypsinogen activation peptide（TAP）,and pathological analysis of the pancreas. The trypsin activity was slightly inhibited at 1.0 and 5.0 mg/m L in GM group and GMTI group,respectively（P〈0.05 vs. P-407）,and completely inhibited at 10.0 and 20.0 mg/m L（P〈0.01 vs. P-407）. After local injection of 10 mg/m L GMTI to rat leg muscular tissue,muscle fiber texture was normal,and there were no obvious red blood cells and infiltration of inflammatory cells. Furthermore,the expression of AMS,CRP and TAP was significantly increased in TP group as compared with control group（P〈0.01）,and significantly decreased in GM group as compared with TP group（P〈0.01）,and also slightly inhibited after 1.0 and 5.0 mg/m L GMTI treatment as compared with TP group（P〈0.05）,and significantly inhibited after 10.0 and 20.0 mg/m L GMTI treatment as compared
文摘Aim: Firstly, to quantify active healthcare professional (HCP) time and costs associated with subcutaneous (SC) administration of trastuzumab (Herceptin?) compared with the standard intravenous infusion (IV) in the treatment of patients with HER2-positive early breast cancer within the adjuvant PrefHer trial setting;secondly, to measure patient time in the care unit and patient infusion chair time for both routes of administration. Methods: A UK multi-centre prospective, observational Time and Motion study was conducted alongside the PrefHer trial (ClinicalTrials.gov id: NCT01401166). Trained observers measured the duration of each SC and IV related task that HCPs undertook and recorded patient time in the chemotherapy unit and infusion chair. The type and quantity of medical consumables used with each route of administration were also collected. Twenty-four patient episodes were recorded (12 SC, 12 IV). Mean total administration time was calculated as the mean sum of task times, both for IV and SC formulations. The mean cost of each route of administration was calculated as the mean cost of HCP time plus the mean cost of consumables used. HCP time was costed using Personal Social Services Research Unit. Consumables were costed using hospital pharmacy data and online sources. Results: Mean active HCP time for IV administration was 92.6 minutes compared with 24.6 minutes for SC administration. The mean cost for IV preparation and administration was ￡144.96 (￡132.05 of HCP time and ￡12.92 of consumables) versus ￡33.15 (￡31.99 of HCP time and ￡1.17 of consumables) for SC administration. Mean time spent in the care unit and in the infusion chair was 94.5 minutes and 75 minutes respectively for IV, and 30.3 minutes and 19.8 minutes for SC. SC administration of trastuzumab could translate to a time saving of 68 minutes (versus IV) with a total cost saving of ￡111.81 per patient episode. This equates to a potential saving of ￡2012.58 over a full course of adjuvant treatment (18 cycles). Conclusion: Subst
