Effects of Diazepam,Phenobarbital,Propranolol,and Cimetidine on Diazepam Oxidizing Isoenzymes in Rat Liver Microsomes

研究地西泮、苯巴比妥、普萘洛尔和西咪替丁对地西泮氧化代谢的影响及其药酶蛋白的初步分析，应用ＨＰＬＣ，ＳＤＳ聚丙烯酰胺凝胶电泳和薄层扫描测定地西泮及其代谢物，并对大鼠肝微粒体和酶蛋白进行分离和含量测定。结果表明地西泮、普萘洛尔和西咪替丁使肝微粒体中Ｐ４５０含量明显降低。地西泮和普萘洛尔明显抑制地西泮Ｃ３羟化活性，大剂量普萘洛尔尚能抑制地西泮Ｎ脱甲基。苯巴比妥明显诱导Ｐ４５０生成，增强地西泮Ｎ脱甲基和Ｃ３羟化酶活性及分子量为５１，０００和５９，０００的电泳蛋白带，而地西泮、普萘洛尔则呈抑制作用。并发现，地西泮Ｎ脱甲基酶活性和分子量为５９，０００蛋白含量呈线性相关（Ｐ＜０．０５），而Ｃ３羟化酶活性则与５１，０００蛋白含量呈线性相关（Ｐ＜０．０１）。因此地西泮Ｃ３羟化代谢可能与５１，０００的Ｐ４５０酶蛋白有关，而Ｎ脱甲基代谢则可能与５９，０００的Ｐ４５０酶蛋白有关。     

环孢素胶丸的药代动力学和相对生物利用度

采用高效液相色谱法进行环孢素胶丸的药代动力学和生物利用度研究，１０名健康志愿者随机交叉单剂量ｐｏ温州第二制药厂和瑞士Ｓａｎｄｏｚ公司的环孢胶丸（２００ｍｇ），其血药浓度－时间曲线均符合一级吸收的双室模型，温州产环孢素胶丸的主要药动学参数ｔ１／２Ｋｄ＝１．０９±０．４６ｈ，ｔ１／２α＝０．３４±０．１５ｈ，ｔ１／２β＝５．１３±１．４１ｈ，ｔｍａｘ＝１．１９±０．１９ｈ，Ｃｍａｘ＝８７８．２±１６７．２ｎｇ／ｍｌ，ＡＵＣ＝４１２７．７±８５４．１ｎｇ·ｈ·ｍｌ－１，其相对生物利用度为（１０４．２±１１．９）％     

主诉腰痛女性患者骨密度和骨质疏松患病率分析

目的研究主诉腰痛女性患者腰椎和髋部骨密度(BMD)测量的临床意义及骨质疏松(OP)患病率。方法采用扇形束双能X线骨密度仪(DEXA)测量主诉为腰痛的女性患者的腰椎和髋部BMD,并与对照组的BMD比较,同时比较其相应骨质疏松(OP)患病率。结果临床主诉以腰痛为主的女性病人腰椎及髋部BMD比以关节痛或全身痛为主诉者的低,(P＜0.05);主诉腰痛者各骨骼部位的OP检出率明显高于关节痛或全身痛者,且均与正常对照组有显著性差异(P＜0.05)。结论骨质疏松是女性腰痛病人就诊的主要原因之一,腰痛患者OP患病率较高;腰椎BMD测定是诊断骨质疏松症的重要手段。     

巴氨西林的人体药代动力学研究

目的建立正常人血浆中巴氨西林浓度的HPLC测定方法,研究巴氨西林在正常人体内的药代动力学行为.方法采用反相高效液相色谱-紫外检测的方法,测定巴氨西林在人体中的主要代谢产物氨苄西林的血药浓度.流动相11mmol/LKH\-2PO\-4(含0.1ml/L冰醋酸)-甲醇(78∶22,v/v).色谱柱为HypersilODS2,5μm,150mm×4.6mmID,紫外检测波长231nm.测定20名男性健康志愿受试者单剂量口服800mg巴氨西林片后血药浓度-时间过程.结果方法的专属性较好,血浆中杂质不干扰样品的测定.方法的回收率大于90%,日间日内变异系数低浓度小于20%,高浓度小于10%,线性范围0.316～20.220μg/ml(r=0.9998,n=5),最低检测浓度0.316μg/ml,符合生物样品分析要求.受试者口服巴氨西林片800mg后,以巴氨西林体内的主要活性代谢产物氨苄西林估算的末端相半衰期(T1/2)1.13±0.31h,峰时间(Tmax)0.81±0.30h,峰浓度(Cmax)10.75±2.53μg/ml,MRT2.01±0.40h,21.25±4.20μg·     

反相高效液相色谱法测定犬血浆中左氧氟沙星浓度及其犬体内药代动力学

目的 :建立测定犬体内左氧氟沙星血药浓度的反相高效液相色谱法 ,并测定其犬体内药代动力学。方法 :以环丙沙星为内标 ,采用 10 %高氯酸为沉淀剂处理犬血浆样品 ,色谱柱为DIKMADiamon silTM C18,5m ,15 0mm× 4 .6mm ,流动相为甲醇 PBS 三乙胺 异丙醇 (33 6 7 0 .14 0 .4 ,用磷酸调pH为 3.0 ) ,流速 1.2ml·min-1,柱温 2 0℃ ,荧光检测(λex=2 95nm ,λem=4 40nm)。结果 :血药浓度线性范围 0 .2 5～ 5 0mg·L-1(r =0 .9998) ,最低检测限浓度为 0 .0 2mg·L-1(S N >3) ,绝对回收率为 83.0 %～85 .6 % (n =5 ) ,方法回收率为 92 .10 %～ 10 6 .77%(n =5 ) ,日内和日间RSD分别为 1.3%～ 4 .0 %和1.8%～ 8.2 % (n =5 )。结论 :本方法简便、灵敏、精密度高 ,重现性好 ,适用于左氧氟沙星犬体内药代动力学研究及生物等效性研究     

遗传代谢病所致贫血的诊疗专家共识

遗传代谢病是一大类复杂的单基因病,由于代谢通路异常导致物质代谢紊乱,可以引起单系统或多系统损害.血液系统疾病涉及红细胞、白细胞和血小板功能和数量的异常,其中贫血最常见,新生儿到老年均可发病.现有研究发现,多种遗传代谢病可导致贫血,致病机制不同,一些疾病引起铁、维生素B12、叶酸代谢异常,另一些造成红细胞膜、代谢相关酶或血红蛋白合成异常,引起不同类型不同程度的贫血.为了提高临床医生对遗传代谢病所致贫血及血液系统疾病的认识,早期诊断、精准治疗、改善预后,国内多学科专家共同讨论,结合国内外经验及指南,以巨幼细胞性贫血、溶血性贫血、铁粒幼细胞性贫血和小细胞低色素性贫血四类贫血相关的遗传代谢病的病因、发病机制、临床表现和治疗为重点,制定了本共识,以期指导优化临床诊治实践.     

Position paper of the ESICM Working Group on Nutrition and Metabolism. Metabolic basis of nutrition in intensive care unit patients: ten critical questions

The metabolic changes associated with critical illness involve several pathways acting at different steps of the utilization of nutritive substrates. The understanding of the role of these pathways and of their complex regulation has led to the development of new strategies for the metabolic and nutritional management of critically ill patients, including the development of new products for nutritional support. The rationale for changing the profile of nutritional support solutions by adding novel substrates is also discussed. This review focuses on the metabolic specificities of critically ill patients and also includes an analysis of the adequacy of tools to monitor the metabolic status and the adequacy of the nutritional support.     

The conduct of in vitro and in vivo drug-drug interaction studies: a PhRMA perspective

Current regulatory guidances do not address specific study designs for in vitro and in vivo drug-drug interaction studies. There is a common desire by regulatory authorities and by industry sponsors to harmonize approaches to allow for a better assessment of the significance of findings across different studies and drugs. There is also a growing consensus for the standardization of cytochrome P450 (CYP) probe substrates, inhibitors, and inducers and for the development of classification systems to improve the communication of risk to health care providers and patients. While existing guidances cover mainly CYP-mediated drug interactions, the importance of other mechanisms, such as transporters, has been recognized more recently and should also be addressed. This paper was prepared by the Pharmaceutical Research and Manufacturers of America (PhRMA) Drug Metabolism and Clinical Pharmacology Technical Working Groups and represents the current industry position. The intent is to define a minimal best practice for in vitro and in vivo pharmacokinetic drug-drug interaction studies targeted to development (not discovery support) and to define a data package that can be expected by regulatory agencies in compound registration dossiers.     

Assessment of vitamin D and calcium status in healthy adult Austrians

BACKGROUND: Because there is reason to assume that also in Austria calcium and vitamin D malnutrition is wide-spread, we initiated a comprehensive study on calcium and vitamin D status in relation to bone health in a large group of the normal adult population. SUBJECTS AND METHODS: We assessed dietary calcium and vitamin D intake, serum concentrations of Ca2+, phosphate, alkaline phosphatase, 25(OH)D, 1,25(OH)2D, parathyroid hormone (PTH), follicle-stimulating hormone (FSH), sex hormones and bone mineral density (BMD) by double-energy X-ray absorptiometry at five different skeletal sites in 648 females and 400 males (age 21-76 years). RESULTS: Mean daily intake of vitamin D (101 IU, range 0.2-320) and calcium (569 mg, range 40-2170) was significantly less than the respective recommended dietary allowances. Two hundred and seventy-one (26%) individuals had hypovitaminosis D with serum 25(OH)D < 12 ng mL(-1), while serum Ca2+ was less than normal in 82 (7.8%) subjects. Multiple regression analysis revealed significant correlations between mean calcium intake and BMD in the femoral region in the men (r = 0.13, P < 0.05) though not in the women. No consistent data could be obtained for associations between BMD and vitamin D status, except for 25(OH)D and BMD at the spine in the men (r = 0.10, P < 0.05). 25(OH)D correlated negatively (P < 0.05) with age in the women (r = -0.11) and with PTH in the women (r = -0.11) and men (r = -0.16). Inversely, a significant (P < 0.001) age-related increase in PTH was observed in both sexes (men, r = 0.19; women, r = 0.14). CONCLUSIONS: Prevalence of hypovitaminosis D in adult Austrians is an imminent risk for development of secondary hyperparathyroidism with advancing age, and requires timely correction of nutritional deficits.     

国产瑞格列奈治疗2型糖尿病的疗效和安全性

目的对国产瑞格列奈(孚来迪)的疗效及安全性进行评价.方法共观察30例2型糖尿病患者,开放性研究,治疗前后自身对照;进行2周清洗期后予国产瑞格列奈1.0 mg,每日3次,为期12周,观察空腹、餐后血糖、糖化血红蛋白、肝肾功能、体重、血脂等的变化.结果与治疗前相比,空腹和餐后血糖及糖化血红蛋白水平均有显著下降(P<0.01),体重增加,肌酐水平升高,但均未超过正常值,肝功能正常.结论国产瑞格列奈有明确的降低空腹、餐后血糖及糖化血红蛋白的效果,不良反应少,是一种安全、有效、价廉的降糖药物.