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61.
René H. Levy Martin S. Dumain James L. Cook 《Journal of pharmacokinetics and pharmacodynamics》1979,7(6):557-578
Equations were derived to describe the time course of drug levels during auto- and heteroinduction under a variety of input conditions. These equations were based on a pharmacokinetic theory of induction which assumes that metabolic clearance increases exponentially to a maximum value and that the rate of this increase is governed by the degradation rate constant of the induced enzyme (k). Closed form solutions could be obtained only for intravenous single-dose (case I) and multiple-dose (case IV) administration. For each of the other cases, constant-rate intravenous infusion (case III), oral single-dose administration (case II), and multiple-dose administration (case V), an exact solution (not closed form) and an approximation (closed form) were derived. Two sets of equations were derived for each of the five cases to take into consideration the possibility of a latency term ().Plots of drug amount X(or concentration C) vs. time (t) were constructed. In case I, a log Xvs. tplot was convex, the slope increasing with time. In case II, Xincreased,reached a peak, and decayed as in case I. In case III ( > 5In 2V/Q) Creached a preinduction steady state before decreasing to a lower (induced) steady state. When =0, Creached a maximum before decreasing to the same induced steady state. The behavior of Cvs. tfor cases IV and V was similar to that for case III. Determination of parameters was attempted in case III. Nonlinear least-square fitting of generated data with 3–9% error yielded reasonable estimates of k.This work was supported by NIH Research Contracts N0l-NS-1-2282 and N01-NS-6-2341.Parts I, II, III, IV, and VI of this series can be found in theJournal of Pharmaceutical Sciences. 相似文献
62.
降纤酶低分子肝素治疗短暂性脑缺血发作的研究 总被引:6,自引:0,他引:6
目的 观察降纤酶与低分子肝素治疗短暂性脑缺血发作的效果及副作用。方法 选择本院神经内科住院患者36例应用降纤酶10U加入加入250ml生理盐水中静脉滴注,隔日1次,共3次;低分子肝素0.5ml脐旁皮下注射,12h 1次,连用7—10d,同时常规给予复方丹参滴注,口服尼莫地平,维生素E,维生素C,停用低分了肝素后给予肠溶阿斯匹林75mg,每日1次口服。结果 治疗开始后TLA发作相继减少,停止发作时间分别为1d内9例,3d内15例,5d内12例。随访6个月—1年,1例2个月后复发,重新应用上药治愈。结论 降纤酶与低分子肝素治疗TLA安全有效、无明显副作用、不易复发。 相似文献
63.
目的 探索一氧化氮供体亚硝基谷胱甘肽(GSNO)能否在体外通过S 亚硝酰化机制激活大鼠肝微粒体谷胱甘肽转移酶 (mGST)。方法 微粒体粗提物与GSNO体外共孵育 ,测定mGST催化动力学改变 ,结合N 乙基马来酰亚胺 (NEM )再激活实验和二巯基苏醇 (DTT)逆转实验 ,以及酶蛋白游离巯基和酶S 亚硝酰化蛋白的改变 ,研究酶的激活机制。结果 GSNO在 0 .12 5~ 2mmol·L- 1浓度范围内呈浓度和时间 (3~ 15min)依赖性地激活mGST ,NEM对酶的再激活效应消失 ,DTT可以逆转上述激活作用 ,同时酶蛋白游离巯基浓度依赖性减少 ,而S 亚硝酰化蛋白浓度依赖性增多。结论 GSNO体外可激活大鼠肝mGST ,激活机制可能与mGST第 4 9位半胱氨酸 (Cys4 9)的巯基被亚硝酰化形成S 亚硝基硫醇结构有关。 相似文献
64.
中药地龙中溶栓成分研究进展 总被引:7,自引:1,他引:7
对近年来国内外地龙中溶栓成分(蚓纤溶酶、蚓激酶、蚓胶原酶)的研究情况进行归纳,介绍了地龙中溶栓成分的性质、分离纯化技术及开发应用状况,并提出了目前研究工作的不足和今后的发展方向。 相似文献
65.
66.
F Chiarelli A Casani A Verrotti G Morgese L Pinelli 《Acta paediatrica (Oslo, Norway : 1992)》1998,87(S425):42-45
Clinical diabetic nephropathy is a well-recognized cause of increased morbidity and mortality in patients with type 1 diabetes. The finding that microalbuminuria predicts progression to overt nephropathy has allowed early diagnosis and preventive interventions. Several studies have demonstrated that treatment with angiotensin-converting enzyme (ACE) inhibitors slows down the rate of decline of the glomerular filtration rate in type 1 diabetes patients with established proteinuria. The renoprotective properties of the ACE inhibitor captopril extend beyond its antihypertensive effects. ACE inhibitors represent the most appropriate class of antihypertensive drugs for treating type 1 diabetes patients because of their efficacy and safety. When microalbuminuria is detected and confirmed in a diabetic child or adolescent, and if it persists despite 6-12 months of improved metabolic control, treatment with ACE inhibitors should be started, even if the child is normotensive. Careful follow-up of renal function is essential. 相似文献
67.
尖吻蝮蛇毒中一种新类凝血酶的分离纯化 总被引:6,自引:1,他引:6
用阴离子交换色谱和凝胶过滤色谱技术,从尖吻蝮蛇毒中纯化得到一个具有凝血活性的组分.经Superdex 75 HR10/30预装柱检测,纯度达99.91%.SDS-PAGE显示为单一条带,还原、非还原条件下分子量分别为59.25k、52.58k.该组分的凝血酶比活为41.5u/mg,精氨酸酯酶比活为14.29u/mg,但不激活血浆凝血因子ⅩⅢ.EDTA不能抑制其凝血活性,而苯甲磺酰氟则产生不可逆抑制作用.结果表明该酶是一种新尖吻蝮蛇毒类凝血酶. 相似文献
68.
广州地区2001年~2003年抗高血压药物利用调查分析 总被引:2,自引:0,他引:2
目的:了解广州地区抗高血压药物的应用情况.方法:采用DDD分析法和金额排序法,对广州地区医院2001年~2003年间抗高血压药购入数据进行综合统计分析.结果:3年来,钙通道阻滞剂所占比例最大,平均为38.98%.其次是血管紧张素转换酶抑制剂(ACEI),平均为31.6%.合资药氨氯地平在DDDs排序及金额排序中均居首位.结论:钙通道阻滞剂、ACEI类药物为抗高血压的主流药,氨氯地平占有重要的临床地位. 相似文献
69.
Vincent Yi-Fong Su Szu-Wen Ko Yuh-Lih Chang Yueh-Ching Chou Hsin-Chen Lee Kuang-Yao Yang Kun-Ta Chou Chia-Chen Hsu 《Allergy, asthma & immunology research》2022,14(3):314
PurposeCurrent clinical guidelines are unclear regarding the association of cardiovascular medication with the risk of acute exacerbation (AE) in patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO).MethodsWe conducted a retrospective cohort study by interrogating the claims database of Taipei Veterans General Hospital. Patients with coexistent fixed airflow limitation and asthma were enrolled as an ACO cohort between 2009 and 2017. Exposure to cardiovascular medications, including angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), non-selective beta-blockers, cardioselective beta-blockers, dihydropyridine (DHP) calcium channel blockers (CCBs), and non-DHP CCBs, in 3-month period each served as time-dependent covariates. Patients receiving a cardiovascular medication ≥ 28 cumulative daily doses were defined as respective cardiovascular medication users. Patients were followed up until December 31, 2018. The primary endpoint was severe AE, defined as hospitalization or emergency department visit for either asthma, COPD, or respiratory failure. The secondary outcome was moderate AE.ResultsThe final study cohort consisted of 582 ACO subjects, with a mean follow-up period of 2.98 years. After adjustment, ARB (hazard ratio [HR], 0.64, 95% confidence interval [CI], 0.44–0.93, P = 0.019), cardioselective beta-blocker (HR, 0.29, 95% CI, 0.11–0.72, P = 0.008) and DHP CCB (HR, 0.66, 95% CI, 0.45–0.97, P = 0.035) therapies were associated with lower risks of severe AE. ARB (HR, 0.42, 95% CI, 0.30–0.62, P < 0.001) and DHP CCB (HR, 0.55, 95% CI, 0.38–0.80, P = 0.002) therapies were associated with lower risks of moderate AE. Cardioselective beta-blockers, ARBs, and DHP CCBs were associated with lower risks of severe AE in frequent exacerbators. ACEI, non-selective beta-blocker, or non-DHP CCB use did not change the risk of severe AE.ConclusionsARB, cardioselective beta-blocker, and DHP CCB therapies may lower the risk of AE in patients with ACO. 相似文献
70.
ACE2基因多态性与原发性高血压的关系 总被引:2,自引:1,他引:1
目的 研究血管紧张素转化酶2(angiotensin converting enzyme 2,ACE2)基因多态性与广东地区原发性高血压的相关性.方法 高血压组选择门诊与住院的汉族无血缘关系的原发性高血压369例,男194例,女175例;对照组为同期体检的广东地区健康汉族居民199例,男101例,女98例.排除冠心病、高血压、糖尿病、脑血管病及肝功能不良、肾功能不良.按照性别分为两组,采用病例对照的原则,应用聚合酶链反应和限制性内切酶片段长度多态性(polymerase chain reaction and restriction fragment length polymorphism,PCR-RFLP)的方法检测ACE2基因G9570A多态性,并随机抽取20份标本进行基因测序以核实基因分型.在分析各亚组的年龄、体重指数、血压及生化指标的基础上综合分析ACE2基因多态性与原发性高血压的关系.结果 高血压组G等位基因频率:男75.3%,对照组男60.4%,差异有统计学意义(χ2=7.0086,P=0.0081),高血压组,女57.4%,对照组45.4%,差异有统计学意义(χ2=6.9443,P=0.0084);女高血压组GG基因型的频率明显高于对照组(χ2=12.9499,P=0.0015);G等位基因人群发生高血压的风险高于A等位基因人群,男OR:1.9945,95% CI:1.1916~3.3385,P=0.0082;女OR:1.603,95% CI:1.1274~2.2792,P=0.0085.结论 ACE2-G9570A多态性与原发性高血压相关;携带G等位基因的男性和仅仅携带G基因的女性人群发生高血压的危险性相对较大,提示ACE2基因可作为原发性高血压的候选易感基因. 相似文献