Objective To investigate the effects ofamiodarone （AMD） on simvastatin （SV） in human liver microsomes and the possible underlying mechanisms. Methods Time-, NADPH- and concentration-dependent inhibitions were test...Objective To investigate the effects ofamiodarone （AMD） on simvastatin （SV） in human liver microsomes and the possible underlying mechanisms. Methods Time-, NADPH- and concentration-dependent inhibitions were tested in HLM. The logarithm of relative inhibition values was plotted versus preincubation time （0, 5, 10, 15, 20min） for a series concentration of AMD used （0, 2, 5, 25, 50 umol/L）, and the slopes determined by linear regression. These slope values represente the observed inactivation rate constants （kobs ）. A double-reciprocal plot was then constructed using the reciprocal of the kobs （y-axis） and the reciprocal of the associated inhibitor concentration （x-axis） to estimate the values of kinact and K1, which were two principal kinetic constants that were specific for mechanism-based inhibition （MBI）.drug-drug interactions （DDI） potential was predicted based on in vitro data and by using the in vitro-in vivo extrapolation. Results The time-, concentration- and NADPH-dependent characteristics confirmed that when SV was the substrate of CYP3A4, the inhibition of AMD to CYP3A4 is MBI. KI and kinact value were calculated to be 5.1umol/L and 0.018minL The CLant of SV was reduced 2.96-5.63 fold when it was administrated with AMD. Conclusion Based on the results, AMD would inhibit SV metabolism via the mechanism-based manner, which would lead to DDI when they are taken together. Careful clinical observation is recommended when AMD and SV have to be simultaneously prescribed.展开更多
Background Metabolic syndrome is known to be a prothrombotic state. We undertook this study to examine a hypothesis that aspirin resistance may be associated with metabolic syndrome, and to assess other potential dete...Background Metabolic syndrome is known to be a prothrombotic state. We undertook this study to examine a hypothesis that aspirin resistance may be associated with metabolic syndrome, and to assess other potential determinants of aspirin resistance in patients with cardiovascular disease （CVD）. Methods A total of 469 elderly patients with CVD were recruited. One hundred and seventy-two patients with metabolic syndrome and 297 without metabolic syndrome （control group） received daily aspirin therapy （〉 75 mg） over one month. Platelet aggregation was measured by light transmission aggregometry （LTA）. Aspirin resistance was defined as 〉 20% arachidonic acid （AA）- and 〉 70% adenosine diphosphate （ADP）-induced aggregation according to LTA. Aspirin semi-responders were defined as meeting one （but not both） of these criteria. Results By LTA, 38 of 469 （8.1%） patients were aspirin resistant. The prevalence of aspirin resistance was higher in the metabolic syndrome group compared with the control group [11.6 % vs. 6.6%, odds ratio （OR） = 2.039; 95% confidence interval （CI）： 1.047-3.973]. In the multivariate logistic regression analysis, metabolic syndrome （OR = 4.951, 95% CI： 1.440-17.019, P = 0.011） was a significant risk factor for aspirin resistance. Conclusions A significant number of patients with CVD and metabolic syndrome are resistant to aspirin therapy. This might further increase the risk of cardiovascular morbidity and mortality in these patients.展开更多
Though the leaders of the new State Investment Corporation （SIC）liave not yet been announced, three names have topped the list of likely candidates：Lou Jiwei,Xie Ping, and Jesse Wang.
文摘Objective To investigate the effects ofamiodarone （AMD） on simvastatin （SV） in human liver microsomes and the possible underlying mechanisms. Methods Time-, NADPH- and concentration-dependent inhibitions were tested in HLM. The logarithm of relative inhibition values was plotted versus preincubation time （0, 5, 10, 15, 20min） for a series concentration of AMD used （0, 2, 5, 25, 50 umol/L）, and the slopes determined by linear regression. These slope values represente the observed inactivation rate constants （kobs ）. A double-reciprocal plot was then constructed using the reciprocal of the kobs （y-axis） and the reciprocal of the associated inhibitor concentration （x-axis） to estimate the values of kinact and K1, which were two principal kinetic constants that were specific for mechanism-based inhibition （MBI）.drug-drug interactions （DDI） potential was predicted based on in vitro data and by using the in vitro-in vivo extrapolation. Results The time-, concentration- and NADPH-dependent characteristics confirmed that when SV was the substrate of CYP3A4, the inhibition of AMD to CYP3A4 is MBI. KI and kinact value were calculated to be 5.1umol/L and 0.018minL The CLant of SV was reduced 2.96-5.63 fold when it was administrated with AMD. Conclusion Based on the results, AMD would inhibit SV metabolism via the mechanism-based manner, which would lead to DDI when they are taken together. Careful clinical observation is recommended when AMD and SV have to be simultaneously prescribed.
文摘Background Metabolic syndrome is known to be a prothrombotic state. We undertook this study to examine a hypothesis that aspirin resistance may be associated with metabolic syndrome, and to assess other potential determinants of aspirin resistance in patients with cardiovascular disease （CVD）. Methods A total of 469 elderly patients with CVD were recruited. One hundred and seventy-two patients with metabolic syndrome and 297 without metabolic syndrome （control group） received daily aspirin therapy （〉 75 mg） over one month. Platelet aggregation was measured by light transmission aggregometry （LTA）. Aspirin resistance was defined as 〉 20% arachidonic acid （AA）- and 〉 70% adenosine diphosphate （ADP）-induced aggregation according to LTA. Aspirin semi-responders were defined as meeting one （but not both） of these criteria. Results By LTA, 38 of 469 （8.1%） patients were aspirin resistant. The prevalence of aspirin resistance was higher in the metabolic syndrome group compared with the control group [11.6 % vs. 6.6%, odds ratio （OR） = 2.039; 95% confidence interval （CI）： 1.047-3.973]. In the multivariate logistic regression analysis, metabolic syndrome （OR = 4.951, 95% CI： 1.440-17.019, P = 0.011） was a significant risk factor for aspirin resistance. Conclusions A significant number of patients with CVD and metabolic syndrome are resistant to aspirin therapy. This might further increase the risk of cardiovascular morbidity and mortality in these patients.
文摘Though the leaders of the new State Investment Corporation （SIC）liave not yet been announced, three names have topped the list of likely candidates：Lou Jiwei,Xie Ping, and Jesse Wang.
