Afatinib is an oral tyrosine kinase inhibitor(TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug ...Afatinib is an oral tyrosine kinase inhibitor(TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug monitoring(TDM) in clinical settings. This study sought to develop a simple and sensitive competitive enzyme-linked immunosorbent assay(ELISA) to quantify afatinib in plasma for routine pharmacokinetic applications. An anti-afatinib antibody was obtained using(S)-N-4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)-quinazoline-4,6-diamine(CTQD), which has the same substructure as afatinib, as a hapten. Enzyme labeling of afatinib with horseradish peroxidase was similarly performed using CTQD. A simple competitive ELISA for afatinib was developed based on the principle of direct competition between afatinib and the enzyme marker for the anti-afatinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Plasma afatinib concentrations below the limit of quantification of 30 pg/mL were reproducibly measurable. Also, the values of plasma afatinib levels measured from 20 patients were comparable with those measured by high-performance liquid chromatography, and there was a strong correlation between the values determined by both methods(Y=0.976 X – 0.207, r=0.975). As indicated by its specificity and sensitivity, this newly developed ELISA for afatinib is an important tool for TDM and studies of the pharmacokinetics of afatinib.展开更多
Congestive heart failure is a disease in which initially compensatory changes in cardiac , vascular, and renal functions become detrimental over time. The changes are mediated by a large number of neurohormones and cy...Congestive heart failure is a disease in which initially compensatory changes in cardiac , vascular, and renal functions become detrimental over time. The changes are mediated by a large number of neurohormones and cytokines. Counter-regulatory hormones also play a role, but are generally insufficient to offset the adverse effects of the neurohormones or progression of the disease. Symptoms of heart failure occurs in the 'presence of systolic dysfunction, usually documented by a decrease in ejection fraction, or can present with impaired diastolic function occasionally labeled as heart failure with preserved systolic function of the left ventricle. Heart failure and its treatment represent a medical problem of significant importance because of the high mortality associated with it despite the current therapy , which has substantial evidence of reduction in mortality and morbidity. Prevention or slowing of the progressive deterioration in function of the heart and other organs involved through utilizing new agents that affect more or different neurohormonal pathways may be beneficial and forms the focus of heart failure research and drug development. However , the multiplicity of hormonal effects mandate the use of complex therapy in the management of congestive heart failure(CHF). The new agents in addition to the conventional therapy used in the management of heart failure are; Human B-type nalriuretic peptide (in the treatment of decompensated CHF) , endothelin receptor antagonists, calcium sensitizers, neutral endopeptidase (NEP) and vasopeptidase inhibitors, vasopressin antagonists and cytokine inhibitors.展开更多
Off-label use is defined by the prescription of a marketed drug outside the conditions described in the summary of product characteristics.In oncology,off-label prescribing of targeted therapies may occur in patients ...Off-label use is defined by the prescription of a marketed drug outside the conditions described in the summary of product characteristics.In oncology,off-label prescribing of targeted therapies may occur in patients with other tumor types expressing the same target.Agents associated to phenotypic approaches such as therapies against the tumoral vasculature(anti-angiogenic drugs) and new immunotherapies(checkpoint inhibitors) also carry the potential of alternative indications or combinations.Off-label use of targeted therapies is little documented and appears to be in the same range than that regarding older drugs with wide variations among agents.When compared with older agents,off-label use of targeted therapies is probably more rational through tumoral genotyping but is faced with a limited clinical support,reimbursement challenges related to the very high pricing and the cost of genotyping or molecular profiling,when applicable.展开更多
胰腺外分泌功能是指胰腺分泌胰酶和胰液.胰酶主要包括脂肪酶、蛋白酶(糜蛋白酶、胰蛋白酶)及淀粉酶.一般而言,慢性胰腺炎迁延近10 a 才会出现脂肪酶分泌减少,而蛋白酶的变化则在15 a 左右.当胰酶分泌量低于正常的10%时,临床上出现脂肪...胰腺外分泌功能是指胰腺分泌胰酶和胰液.胰酶主要包括脂肪酶、蛋白酶(糜蛋白酶、胰蛋白酶)及淀粉酶.一般而言,慢性胰腺炎迁延近10 a 才会出现脂肪酶分泌减少,而蛋白酶的变化则在15 a 左右.当胰酶分泌量低于正常的10%时,临床上出现脂肪痢、粪中氮质增加、腹痛,淀粉吸收不良,其中以脂肪痢较突出.长期的吸收障碍将导致体重减轻。展开更多
文摘Afatinib is an oral tyrosine kinase inhibitor(TKI) approved for treating advanced non-small cell lung cancer. It is necessary to develop a simple quantification method for TKIs in order to facilitate therapeutic drug monitoring(TDM) in clinical settings. This study sought to develop a simple and sensitive competitive enzyme-linked immunosorbent assay(ELISA) to quantify afatinib in plasma for routine pharmacokinetic applications. An anti-afatinib antibody was obtained using(S)-N-4-(3-chloro-4-fluorophenyl)-7-(tetrahydrofuran-3-yloxy)-quinazoline-4,6-diamine(CTQD), which has the same substructure as afatinib, as a hapten. Enzyme labeling of afatinib with horseradish peroxidase was similarly performed using CTQD. A simple competitive ELISA for afatinib was developed based on the principle of direct competition between afatinib and the enzyme marker for the anti-afatinib antibody, which had been immobilized on the plastic surface of a microtiter plate. Plasma afatinib concentrations below the limit of quantification of 30 pg/mL were reproducibly measurable. Also, the values of plasma afatinib levels measured from 20 patients were comparable with those measured by high-performance liquid chromatography, and there was a strong correlation between the values determined by both methods(Y=0.976 X – 0.207, r=0.975). As indicated by its specificity and sensitivity, this newly developed ELISA for afatinib is an important tool for TDM and studies of the pharmacokinetics of afatinib.
文摘Congestive heart failure is a disease in which initially compensatory changes in cardiac , vascular, and renal functions become detrimental over time. The changes are mediated by a large number of neurohormones and cytokines. Counter-regulatory hormones also play a role, but are generally insufficient to offset the adverse effects of the neurohormones or progression of the disease. Symptoms of heart failure occurs in the 'presence of systolic dysfunction, usually documented by a decrease in ejection fraction, or can present with impaired diastolic function occasionally labeled as heart failure with preserved systolic function of the left ventricle. Heart failure and its treatment represent a medical problem of significant importance because of the high mortality associated with it despite the current therapy , which has substantial evidence of reduction in mortality and morbidity. Prevention or slowing of the progressive deterioration in function of the heart and other organs involved through utilizing new agents that affect more or different neurohormonal pathways may be beneficial and forms the focus of heart failure research and drug development. However , the multiplicity of hormonal effects mandate the use of complex therapy in the management of congestive heart failure(CHF). The new agents in addition to the conventional therapy used in the management of heart failure are; Human B-type nalriuretic peptide (in the treatment of decompensated CHF) , endothelin receptor antagonists, calcium sensitizers, neutral endopeptidase (NEP) and vasopeptidase inhibitors, vasopressin antagonists and cytokine inhibitors.
文摘Off-label use is defined by the prescription of a marketed drug outside the conditions described in the summary of product characteristics.In oncology,off-label prescribing of targeted therapies may occur in patients with other tumor types expressing the same target.Agents associated to phenotypic approaches such as therapies against the tumoral vasculature(anti-angiogenic drugs) and new immunotherapies(checkpoint inhibitors) also carry the potential of alternative indications or combinations.Off-label use of targeted therapies is little documented and appears to be in the same range than that regarding older drugs with wide variations among agents.When compared with older agents,off-label use of targeted therapies is probably more rational through tumoral genotyping but is faced with a limited clinical support,reimbursement challenges related to the very high pricing and the cost of genotyping or molecular profiling,when applicable.
文摘胰腺外分泌功能是指胰腺分泌胰酶和胰液.胰酶主要包括脂肪酶、蛋白酶(糜蛋白酶、胰蛋白酶)及淀粉酶.一般而言,慢性胰腺炎迁延近10 a 才会出现脂肪酶分泌减少,而蛋白酶的变化则在15 a 左右.当胰酶分泌量低于正常的10%时,临床上出现脂肪痢、粪中氮质增加、腹痛,淀粉吸收不良,其中以脂肪痢较突出.长期的吸收障碍将导致体重减轻。
