Serum glycoside concentrations after single or repeated intravenous doses ofβ-methyl-digoxin and digoxin

Summary The aim of the present investigation was to estimate the ratio of the intravenous doses of-methyl-digoxin and digoxin required to produce identical serum glycoside concentrations in man.20 patients on intravenous maintenance therapy were changed from-methyl-digoxin to the identical dose of digoxin or vice versa. Each drug was given for 7 days. Serum concentrations 13% higher were found during administration of-methyl-digoxin. Assuming a half life of 60 h after with drawal, the dose of digoxin producing the same minimum serum concentration was estimated to be 1.16 times higher than that of-methyl-digoxin.18 healthy volunteers received 0.4 mg -methyldigoxin, and 23 the same dose of digoxin, as an intravenous infusion over 2 h. The serum concentrations and urinary glycoside excretion were measured over a period of 32 hrs. During the first hour after the infusion the serum concentration of digoxin declined more rapidly than that of-methyl-digoxin. Thereafter, the ratio of the serum concentrations did not change appreciably up to the end of the investigation. The area under the serum concentration/time curve was about 13% greater for-methyl-digoxin than for digoxin; this difference was not significant.The average renal clearance was 96±9 ml for-methyl-digoxin, 151±13 ml for digoxin. Since the total body clearance of digoxin is only about 1.16 times higher than that of-methyl-digoxin, the lower renal clearance of-methyl-digoxin must partly be compensated by higher extrarenal clearance.From the ratios of the areas under the serum concentration/time curves after single doses of -methyldigoxin and digoxin, and the minimum serum concentrations during maintenance therapy, it was concluded that the dose of digoxin to produce the same average serum concentrations would be about 1.15 times higher than that of-methyl-digoxin. In comparison with the large variations in individual dosage of digoxin and-methyl-digoxin, this difference is too small to be of practical importance.     

Absorption of β-methyl-digoxin determined after a single dose and under steady state conditions

Summary Single doses of -methyl-digoxin 0.4 mg were given to groups of 17 – 18 healthy volunteers as an intravenous infusion lasting 2 hours, or orally as Lanitop Liquidum^® or Lanitop^® tablets. The serum glycoside concentration and urinary glycoside excretion were measured over 8 and 32 h. The absolute bioavailability from the oral preparations in comparison with the infusion was lower for the first 8 h than for the entire 32 h of the investigation; the relative bioavailability from tablets was the same as from the solution for both periods. For both periods the area under the serum concentration/time curve and the urinary glycoside excretion were significantly lower after administration of the tablets than after intravenous infusion. Taking the average of both parameters, the absolute bioavailability of -methyl-digoxin was about 80% from the solution and about 70% from the tablets. In 18 patients undergoing intravenous or oral therapy with -methyl-digoxin steady state glycoside concentrations were compared in a cross-over study of intravenous maintenance therapy with Lanitop^® ampoules or oral treatment with Lanitop^® tablets. For a standard daily dose of 0.2 mg -methyl-digoxin the serum concentrations were 1.35±0.10 ng/ml during both intravenous and oral administration. The intra-individual variation in glycoside concentration after changing from intravenous to oral maintenance therapy, or vice versa, was about the same as during continued intravenous or oral administration. It is concluded that the rate of rise of serum concentration after a single dose may be a useful indicator of the rate of absorption, but that the area under the serum concentration/time curve and the urinary glycoside excretion up to 32 h are unsuitable for determining equivalent doses of different formulations or routes of administration of digitalis glycosides.     

β-Adrenoceptor polymorphisms

There can be no doubt that ₁-, ₂- and ₃-adrenoceptor genes have genetic polymorphisms. Two single nucleotide polymorphisms have been described for the ₁- (Ser49Gly; Gly389Arg), three for the ₂- (Arg16Gly; Gln27Glu; Thr164Ile) and one for the ₃-adrenoceptor subtype (Trp64Arg) that might be of functional importance. The possibility that changes in expression or properties of the -adrenoceptors due to single nucleotide polymorphisms might have phenotypic consequences influencing their cardiovascular or metabolic function or may contribute to the pathophysiology of several disorders like hypertension, congestive heart failure, asthma or obesity is an idea that has attracted much interest during the last 10 years. At present, it appears that these -adrenoceptor polymorphisms are very likely not disease-causing genes, but might be risk factors, might modify disease and/or might influence progression of disease. The aim of this review is to provide an overview of the functional consequences of such -adrenoceptor polymorphisms in vitro, ex vivo and in vivo.     

β-干扰素

异名人成纤维细胞干扰素(Interferon-human Fibroblast)、HF—IF B-IF Fiblaferon,Feron 化学名为人成纤维细胞受诱导剂作用后产生的分子量约22,000的糖蛋白。与糖链结合的由166个氨基酸组成的多肽部分,分子式为C_(908)H_(1406)N_(246)O_(252)S_7,分子量为20,025。包含糖链后分子量约为22,000。药效分类抗肿瘤、抗病毒药开发单位 (美)Searle 上市厂商 (西德)Bioferon 1984年1月     

β-LACTAMASE INHIBITORS

It is now well established that among the penicillins and cephalosporins,one of the most important mechanisms of resistance is the production of theenzyme,β-lactamase.This enzyme is widely distributed among Gram-positiveand Gram-negative bacteria and in recent years the frequency of β-lactamaseproducing strains in many important pathogens bas increased significantly.Table 1 shows the frequency of penicillin-resistant Staphylococcusanreus in the Outpatients Department of one London hospital. It willbe seen that more than 80％ of these isolates are now penicillin-resistantwhich means they are also resistant to ampicillin,amoxycillin and to otherpenicillins.No longer can we say that β-lactamase-producing Staph.aureusare confined to the hospital.     

β抑制蛋白

上海两名科学家经过长期合作，在CD4^＋T细胞中发现一种称为β抑制蛋白（β-arrestin 1）的蛋白质，可使该细胞寿命延长，而且不会凋亡。CD4^＋T细胞在获得性免疫中很重要，如果失调，会导致自身免疫疾病。[第一段]     

β-Adrenoceptor studies

Summary Propranolol, pindolol, practolol and metoprolol were investigated for -adrenoceptor blocking activities in the guinea-pig right atrium and tracheal strip preparation, both in the absence and presence of 2.8% bovine serum albumin. Similarly, the influence of 2.8% albumin on the antagonism of ouabain-induced arrhythmias in the guinea-pig right atrium was studied. Local anesthetic activities were measured on the isolated, partially desheathed, frog sciatic nerve.Incubation with albumin decreased the in vitro atrial -adrenoceptor blocking potency of propranolol against (-)-isoprenaline-induced positive chronotropism by a factor of 12 whereas the activity on tracheal receptors was 4.5 times lower. The activities of pindolol, practolol and metoprolol both on atrial and tracheal -receptors were not significantly influenced by the presence of albumin. The results demonstrate the important role of albumin binding in causing differences in the in vivo and in vitro cardiac -adrenoceptor blocking potency ratios of propranolol compared to the other -receptor antagonists studied.The large difference between -adrenoceptor blocking and minimal antiarrhythmic concentrations, the approximately 1000 times lower antiarrhythmic activity of practolol compared to propranolol and the very significant correlation between the antiarrhythmic and local anesthetic activities demonstrate that the antagonism of ouabain-induced arrhythmias in the isolated right atrium of the guinea pig is solely due to the membrane-stabilizing properties of the -receptor antagonists. The moderate decrease of the antiarrhythmic potency of propranolol by 2.8% albumin was concluded to have no relevance for the in vivo situation.Binding to 2.8% albumin was investigated using the ultracentrifugation technique. For propranolol a linear relationship was found between log concentration and percent binding which amounted to 88.2% at 10^–6 M. In contrast, protein binding of pindolol, practolol and metoprolol was low and concentration independent.     

新型β-内酰胺抗生素及β-内酰胺酶抑制剂

本文综述了新型β-内酰胺抗生素和β-内酰胺酶抑制剂的发展趋向。文章分(1)具有新型母核的β-内酰胺抗生素,(2)新的头孢菌素衍生物,(3)β-内酰胺酶抑制剂三个方面,通过对青霉素与头孢菌素两大类抗生素的结构与生物活性之间的关系研究,从而发展了青霉烯类衍生物、碳杂青霉烯衍生物(如硫霉素)、氧杂青霉烯衍生物、碳杂和氧杂头孢菌素以及单环β-内酰胺抗生素(如诺卡霉素)等过程进行了阐述。同时择要介绍了一些主要的已经应用于临床或将应用于临床的新β-内酰胺类抗生素和β-内酰胺酶抑制剂。本文引用主要参考文献64篇。     

β1—选择性β阻滞剂老年高血压的治疗

由于目前提供医药治疗的可能性，人类的平均寿命逐渐延长。与此相关，老年病发病率也在不断上升。大部分老年人患高血压、冠心病和由此产生的心功能不全。为了提高生活生活质量和降低疾病的严重程度，必须进行及时和适当的治疗。首先使用β受体阻滞剂、特别是在此期间上市的β１选择性药物，它们与非选择性β受体阻滞剂相比，具有较好的作用和轻微的副作用特点。     

45例少见β地中海贫血患者β球蛋白基因序列分析

目的研究佛山地区稀有β地中海贫血基因突变。方法对来佛山妇幼保健院产前检查的8400例患者进行血细胞和血红蛋白电泳常规筛查．对其中3600例血象异常怀疑β地中海贫血的患者行反向点杂交检测常见的17种突变,确诊1260例,然后对未发现常见突变的45例可疑患者扩增β球蛋白基因送公司直接基因测序。结果发现了15例稀有β地中海贫血,其中nt-90（C→T）、CD6（GAG→AAG）突变各2例,IVS—Ⅰ-116（T→G）、IVS—Ⅰ-128（T→G）、IVS—Ⅰ-130（G→C）突变各1例,CD113（GTG→GAG）突变8例。结论针对未发现常见17种β地中海贫血基因突变的可疑患者采用β球蛋白基因直接基因测序鉴定可以发现稀有突变,并为患者更好地提供产前基因诊断服务。     

β—内酰胺抗生素和β—内酰胺酶抑制剂的筛选

自从青霉素引入医疗实践以来,β-内酰胺抗生素就成为最重要的化学治疗剂类别之一。这类抗生素对于细胞壁的生物合成具有特殊的抑制能力,而动物没有细胞壁,这就保证了它们对人的低毒性。1929年 Alexandex Fleming 在一个青霉菌落与周围的细菌培养物之间观察到抗菌作用。后来被 Florey 等人证明了 Fleming 实验的抗菌物质是青霉素。这是第一次发现β-内酰胺抗生素,也是第一次发现抗生素。这为开发许多其它抗生     

β-HCG的研究进展

人绒毛膜促性腺激素(β-HCG)是由合体滋养细胞合成的糖蛋白激素,目前被广泛应用于临床妊娠的诊断和其他疾病的诊断、疗效评估及预后评价等方面,现将β-HCG的研究进展综述如下。     

β—内酰胺酶抑制剂

过去的40多年是β-内酰胺抗生素类发展取得空前成就的时期.天然、半合成和新合成的药物不断涌现.同时,为了寻找新的和改进的β-内酰胺抗生素,已开展了酶与这些分子相互作用的研究.70年代开发成功的酶抑制剂已在临床上应用.     

β阻滞剂Soquinolol Mucate

合成将5-羟基-1,2,3,4-四氢异喹啉用甲酰胺在140℃下进行甲酰化反应,得N甲酰基-5-羟基-1,2,3,4-四氢异喹啉(Ⅲ),Ⅲ在水中通过NaOH与氯甲基环氧乙烷缩合得N-甲酰基-5-(2,3-环氧丙氧基)-1,2,3,4-四氢异喹啉(Ⅴ),最后将Ⅴ与特丁胺(Ⅵ)缩合即得。药理作用本品是一个强效的非亚型选择性的β肾上腺素能受体阻滞剂,不具内源性拟交感活性。尽管在体外结合试验和豚鼠兰根道尔夫氏心脏标本试验中,本品与心得     

β-阻滞剂 Arotinolo-HCI

异名 Almarl 化学名 5-[2-[(3-叔丁基氨基-2-羟基丙基)硫]-4-噻唑基]2-噻吩羧酰胺盐酸盐药效分类β阻滞剂开发单位 (日本)住友制药株式会社上市厂商 (日本)住友制药株式会社1985年12月首次上市药理本品是具有适度α阻滞作用的β阻滞药。其β阻滞作用为非选择性的。其阻滞作用比心得安强,并且持续时间长。本品无膜安定作用及内源性拟交感作用。拉贝洛尔的α、β阻滞作用比率为1∶3,而本品是1∶8,因此本品无拉贝洛尔的直立性低血压     

β-内酰胺酶抑制剂

众所周知,细菌对青霉素类和头孢菌素类耐药的最重要的机制之一是产生β-内酰胺酶。这种酶广泛地存在于革蓝氏阳性和阴性细菌中。近年来,许多重要的病原菌中产β-内酰胺酶菌株明显增加。表1列出伦敦一家医院从门诊病人分离出的耐药金葡菌出现的频率。从中看出,分离菌株中已有80％以上     

β-内酰胺类抗生素

近年虽已开发一些新青霉素和新头孢菌素,但与临床要求广谱、低毒和高效的理想抗生素还有差距。例如替卡西林(Ticarcillin)虽较广谱,但对多数葡萄球菌、肠球菌和克雷氏菌耐药。第二代头孢菌素对耐药嗜气革兰氏阴性菌和肠球菌均无效。头孢噻肟(Cefotaxime)和头孢唑肟(Ceftizoxime)对绿脓杆菌的作用均不够理想,对厌氧菌如拟杆菌属无效;头孢哌酮对绿脓杆菌较好,但对拟杆菌效果不佳,大部分经胆排泄,容易引起腹泻;头孢西啶(Ceftazi-