联用依普拉封和低剂量的雌激素治疗绝经后骨质疏松症

1概况异丙氧黄酮（依普拉封，IpPriflavone）是一种合成的异黄酮衍生物（7一异丙氧基异黄酮），60年代后期匈牙利合成，作为饲料添加剂，1988年日本最先开始作为治疗骨质疏松药（日本武田药品工业株式会社生产），我国正处试用阶段（武汉滨湖制药厂生产）。1．l作用：依普拉封主要抑制骨吸收一’］，在不同实验模型中它能直接抑制破骨细胞活性。依普拉封是一种非激素类化合物，但能增强雌激素刺激甲状腺释放降钙素的作用，使血钙降低。依普拉封还可能刺激成骨细胞的活性，对成骨细胞的增生也有轻度的刺激作用，能减少甲状旁腺激素引起的人…     

Five Isoflavonoid Compounds from the Roots of Caragana sinica

从豆科植物锦鸡儿Ｃａｒａｇａｎａｓｉｎｉｃａ的根（中药金雀根）中分得５个异黄酮类成分，分别鉴定为ｆｌｅｍｉｃｈａｐｐａｒｉｎＢ（１）；５羟基７甲氧基３′，４′二氧亚甲基异黄酮（２）；５羟基７，４′二甲氧基异黄酮（３）；芒柄花素ｆｏｒｍｏｎｏｎｅｔｉｎ（４）和赝靛黄素ｐｓｅｕｄｏｂａｐｔｉｇｅｎｉｎ（５）。其中化合物２为新的天然异黄酮化合物。     

金雀异黄酮对骨质疏松后骨折大鼠作用的实验研究

目的 观察金雀异黄酮对实验性骨质疏松后骨折大鼠的骨密度（bone mineral density，BMD）和血清骨代谢生化指标的影响。方法 采用SD雌性大鼠去双侧卵巢8周后建立骨质疏松后骨折模型，给予金雀异黄酮及雌二醇灌胃．分别于骨折后7天、14天、28天监测大鼠骨折段骨密度及其形态学改变，检测血清骨碱性磷酸酶（ALP）、血清钙（Ca）、血清磷（P）等骨代谢生化指标。结果 骨质疏松后骨折大鼠采用金雀异黄酮治疗后骨密度明显升高，且形成骨痂较多．与阴性对照组的差异具有统计学意义（P〈0、05），与雌二醇组无显著性差异。雌二醇组和金雀异黄酮组血清ALP活性低于阴性对照组。结论 金雀异黄酮能促进骨质疏松后骨折的愈合。     

金雀根中的异黄酮类成分

从豆秋植物锦鸡儿Caragana sinica的根（中药金雀根）中分得5个异黄酮类成分，分别鉴定为flemichapparin B(1);5-羟基－7－甲氧基－3′，4′－二氧亚甲基异黄酮（2）；5－羟基－7，4′－二甲氧基异黄酮（3）；芒柄花素formononetin(4)和赝靛黄素pseudobaptigenin(5)；其中化合物2为新的天然异黄酮化合物。     

金雀异黄素4′-二氟甲醚化衍生物的合成

目的 合成金雀异黄素4′-二氟甲醚化衍生物。方法 金雀异黄素与HCF2Cl、NaOH在水和二氧六环的混合液中发生二氟甲醚化反应，生成7，4′-二-二氟甲氧基-5-羟基异黄酮（2）、7-二氟甲氧基-5，4′_二羟基异黄酮（3）和4′-二氟甲氧基-5，7-二羟基异黄酮（4），再经甲醚化反应得到7-二氟甲氧基-5，4′-二甲氧基异黄酮（5）和4′-二氟甲氧基-5，7-二甲氧基异黄酮（6）。结果 化合物的结构经MS、^1H-NMR、^13C-NMR、^19F-NMR等进行了确证，化合物（4）和（6）为首次合成的新化舍物。结论 为金雀异黄素4′-二氟甲醚化衍生物的合成提供了实验基础。     

膜荚黄芪毛状根中异黄酮成分的反相高效液相色谱分析

对膜荚黄芪毛状根中６种异黄酮成分进行了反相高效液相色谱法测定。色谱柱为ＮｕｃｌｅｏｓｉｌＣ１８柱，流动相为甲醇—水（３∶２和３∶１，ｖ／ｖ），检测波长为２５４ｎｍ和２８０ｎｍ。６种异黄酮成分为：１０羟基３，９二甲氧基紫檀烷，（３Ｒ）８，２’二羟基７，４’二甲氧基异黄烷，芒柄花素（７羟基４’甲氧基异黄酮），８，３’二羟基７，４’二甲氧基异黄酮，２’羟基３’，４’二甲氧基异黄烷７Ｏ葡萄吡喃糖甙，毛蕊异黄酮（７，３’二羟基４’甲氧基异黄酮）。异黄酮浓度在２５～１２５μｇ范围内与峰面积有良好的线性关系；加样回收率为９６４７％～１０３３３％；精密度试验相对标准偏差为２５７％～６５２％；测得黄芪毛状根中６种异黄酮成分的含量在００００５％～０００６５％之间。     

紫外分光光度法测定大豆异黄酮胶囊中大豆异黄酮含量

目的 建立以紫外分光光度法测定大豆异黄酮胶囊中大豆异黄酮含量的方法。方法 采用紫外分光光度法，检测波长为262nm。结果 大豆异黄酮浓度在9．73～19．46μg／mL范围内与吸光度线性关系良好（r=0．9998），平均回收率为99．76％（RSD=O.64％）。结论 该方法准确可靠，操作简便，稳定性好。     

腹腔镜与开腹手术治疗异位妊娠的临床效果对照

目的：对比腹腔镜与开腹手术治疗异位妊娠的效果，比较两种治疗方法的优缺点。方法选择我院2013年1月~2014年10月收治的异位妊娠患者100例为研究对象，其中59例采取腹腔镜手术终止妊娠（腹腔镜组），41例采取开腹手术终止妊娠（开腹手术组），对比治疗效果。结果腹腔镜组和开腹手术组的手术时间分别为（45.6依10.2）、（68.5依9.4）min，术中失血量分别为（21.2依9.6）、（56.2依26.1）ml，下床活动时间分别为（5.6依1.8）、（25.2依4.7）h，排气时间分别为（8.4依2.3）、（25.6依9.8）h，住院时间分别为（3.1依0.6）、（6.7依1.2）d，两组比较差异均有统计学意义（P<0.05）。结论腹腔镜异位妊娠术后创伤小，恢复快，通过积极的综合治疗措施能达到较开腹手术更好的治愈效果，值得加以推广。     

多序岩黄芪化学成分研究多序岩黄芪化学成分研究

目的研究多序岩黄芪的化学成分。方法用柱色谱分离，用理化性质及波谱方法鉴定结构。结果从多序岩黄芪中分离鉴定了5个化合物：红芪木脂素A（1），异甘草素（2），7-羟基-4′-甲氧基异黄酮（3），毛蕊异黄酮（4）和芒柄花素（5）。结论化合物1为新化合物，命名为红芪木脂素A。     

黄芪中主要异黄酮苷及其苷元的含量分析

采用高效液相色谱-二极管阵列检测器（HPLC/DAD）方法测定黄芪药材和饮片中主要异黄酮苷及其苷元的含量,并采用高效液相质谱联用技术（LC/MS^n）鉴定主要未知色谱峰的结构。测定了黄芪药材及饮片中2个主要异黄酮苷：毛蕊异黄酮苷（1）,芒柄花苷（2）及其相应苷元毛蕊异黄酮（3）,芒柄花素（4）的含量,并鉴定了两个主要未知色谱峰的结构分别为毛蕊异黄酮苷6′″-O-丙二酸酯（U1）和芒柄花苷6′″-O-丙二酸酯（U2）。结果表明黄芪药材中异黄酮苷类成分的含量高于饮片,而苷元含量则低于饮片。另外,将黄芪药材粉末用水润湿后在35℃放置24小时,其中的异黄酮苷及其丙二酸酯类成分几乎全部转变成了苷元。黄芪中异黄酮苷类成分在一定条件下可转化为苷元,异黄酮苷和苷元在黄芪药材与饮片中含量的不同可能与饮片制备过程中苷类成分的酶解有关。     

高效液相色谱法测定人血清和尿中盐酸青藤碱浓度及药代动力学研究

用RP-HPLC法,以三唑仑为内标,反相C₁₈为分析柱,乙腈—0.01mol·L^-1磷酸二氢钠—四甲基乙二胺(46∶54∶0.22v/v)为流动相,磷酸调至pH6.9,检测波长263nm,测定血清和尿中盐酸青藤碱浓度,线性范围分别为6～480ng·mL^-1和0.06～3μg·mL^-1,平均回收率75.88%和91.35%,日内日间误差小于5%,最低检测浓度血清4ng·mL^-1,尿40ng·mL^-1。8名健康男性志愿者单次口服盐酸青藤碱片80mg,测定血清及尿浓度,该药符合二室开放模型,体内消除符合一级动力学消除过程,主要药代动力学参数:T_1/2α0.791±0.491h,T_1/2β9.397±2.425h,T_{max 1.040±0.274h,Cmax246.604±71.165ng·mL^-1,AUC 2651.158±1039.050ng·h·mL^-1,CL 0.033±0.01ng·mL^-1。}     

Relative bioavailability of a new oral form of cyclosporin A in patients with rheumatoid arthritis.

The relative bioavailability of cyclosporin A (CsA) from a new microemulsion oral formulation (NEO) and the currently used soft gelatine capsule (SGC) was determined at steady state in 12 patients with rheumatoid arthritis. The AUC(0,12 h) values of cyclosporin A were significantly greater after NEO than SGC (2873 +/- 848 ng ml-1 h (mean +/- s.d.) vs 2355 +/- 1128 ng ml-1 h; P = 0.02, 95% CI (confidence interval of the difference: 81 to 955 ng ml-1 h). Cmax values were significantly higher after NEO than after SGC (811 +/- 244 ng ml-1 vs 495 +/- 291 ng ml-1, P < 0.0001, 95% CI of the difference: 209 to 422 ng ml-1).     

CYP3A4 and CYP2A6 activities marked by the metabolism of lignocaine and coumarin in patients with liver and kidney diseases and epileptic patients.

1. The in vitro hepatic metabolism of lignocaine to monoethylglycinexylide (MEGX) is mediated by CYP3A4 and that of coumarin to 7-hydroxycoumarin (7OHC) by CYP2A6. We investigated the usefulness of monitoring serum MEGX concentrations (after 1 mg kg-1 lignocaine i.v.) and urinary 7OHC excretion (after 5 mg coumarin p.o.) to reflect liver function in patients with liver (n = 36), kidney (n = 12) and epileptic (n = 12) disease and in control subjects (n = 20). The extent of liver disease was assessed using measurements of serum aminoterminal propeptide (PIIINP) and Child-Pugh grades. 2. Serum concentrations of MEGX were decreased in severe (4.6 +/- 3.0 s.d. ng ml-1), moderate (19.1 +/- 11.6 s.d. ng ml-1) and mild (32.8 +/- 14.2 s.d ng ml-1) liver disease as compared with controls (53.4 +/- 15.8 s.d ng ml-1). The excretion of 7OHC over 2 h was decreased in severe (18.0 +/- 10.3 s.d % of dose) and moderate (34.2 +/- 15.6 s.d %), but not in mild (49.7 +/- 19.0 s.d %) liver disease as compared with that in controls (56.2 +/- 11.6%). 3. In epileptic patients the urinary recovery of 7OHC was increased (2 h value 69.5 +/- 13.2 s.d %) suggesting enzyme induction. In contrast, serum MEGX concentration were low (40.0 +/- 14.1 s.d ng ml-1), possibly due to competition for CYP3A4 between lignocaine and antiepileptic drugs. 4. In patients with kidney disease serum MEGX concentration (56.5 +/- 26.1 s.d ng ml-1) was similar to that in controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetic-pharmacodynamic model for fantofarone cardiac and brachial haemodynamic effects in healthy volunteers

AIMS: To investigate the pharmacokinetics of SR 33671, the main active metabolite of the calcium antagonist fantofarone, and the relationships between its concentrations and pharmacodynamic effects after a single oral administration of two doses (100 and 300 mg) of fantofarone. METHODS: A placebo-controlled, randomized, double-blind and crossover study was performed in six healthy volunteers. SR 33671 plasma concentrations (C, ng ml-1 ) and effects (E) on heart rate (HR, beats min-1 ), PR interval duration (ms), brachial artery flow (BAF, ml min-1 ) and brachial vascular resistance (BVR, mmHg s ml-1 ) were determined repeatedly after drug intake. Haemodynamic effects were expressed as percent changes from initial values. Bi-exponential (pharmacokinetics), and linear [E=S.C+E0, for cardiac effects] or sigmoid [E=Emax.Cgamma/(CEgamma50+Cgamma ), for haemodynamic effects] models were fitted to individual data. RESULTS: Peak plasma concentrations and areas under the curve up to 24 h were (mean+/-s.d.) 16+/-10 ng ml-1 and 157.50+/-89.13 ng ml-1 h, and 63+/-11 ng ml-1 and 535.50+/-135.11 ng ml-1 h, after 100 and 300 mg, respectively. Terminal half-life was approximately 4 h. For pharmacodynamics, we obtained: S=-0.201+/-0.057 beats min-1/ng ml-1 for HR, S=0.526+/-0.114 ms/ng ml-1 for PR interval duration, Emax=42+/-6%, CE50=8.8+/-7.2 ng ml-1 and gamma=2.2+/-1.5 for BAF, and Emax=-28+/-4%, CE50=5.8+/-5.1 ng ml-1 and gamma=3.4+/-1.8 for BVR. At a SR 33671 concentration of 15 ng ml-1, BVR is decreased by 27% whereas HR is reduced by less than 3 beats min-1 and PR interval duration is increased by less than 8 ms. CONCLUSIONS: Fantofarone is able to induce submaximal peripheral vasodilating effects at doses that are devoid of any clinically significant cardiac effect.     

Fosinopril/hydrochlorothiazide: single dose and steady-state pharmacokinetics and pharmacodynamics

AIMS: Fosinoprilat, the active product of fosinopril, is eliminated by an hepatic pathway in addition to the renal pathway shared by other angiotensin converting enzyme inhibitors (ACEIs). This study aimed to determine whether impaired renal function affects the pharmacokinetics and pharmacodynamics of a combination of fosinopril and hydrochlorothiazide (HCTZ). METHODS: The study had a parallel-group design comparing patients with renal impairment and body-mass-index-matched normal controls. The study was done in a University clinic in 13 patients with renal impairment (mean creatinine clearance 55.7+/-15.6 ml min-1 1.73 m-2 ) and 13 age-, sex-, and body-mass-index-matched normal controls (mean creatinine clearance 102.4+/-8.9 ml min-1 1.73 m-2 ). All patients and normal controls received fosinopril sodium 20 mg and HCTZ 12.5 mg as a daily oral administration on days 1-5. Non-compartmental pharmacokinetic parameters of fosinoprilat and HCTZ were determined from blood and urine samples obtained over 48 h starting on Day 1 (single dose) and Day 5 (steady state): maximum serum concentration (Cmax ), time to maximum serum concentration (tmax ), area under the serum concentration-time curve during the dosing interval (AUC), cumulative urinary excretion (CUE) and the accumulation index (AI; ratio of AUC-day 5/AUC-day 1). Pharmacodynamic parameters were also measured over 24 h on day 1 and over 48 h on day 5: serum ACE activity and arterial blood pressure. RESULTS: Fosinoprilat pharmacokinetic parameters on day 1 in renally impaired vs normal patients: Cmax=387+/-0.19 vs 324+/-0.25 ng ml-1 (P=0.07); tmax=3.5 vs 3.0 h (P=0.58); AUC=3510+/-0.29 vs 2701+/-0.35 ng ml-1 h (P=0. 072); CUE=5.08+/-2.70 vs 7.40+/-2.56% (P=0.009). Fosinoprilat parameters on day 5: Cmax=517+/-0.40 vs 357+/-0.19 ng ml-1 (P=0. 007); tmax=3.0 vs 3.0 h (P >0.99); AUC=4098+/-0.43 vs 2872+/-0.30 ng ml-1 h (P=0.027); CUE=6.81+/-3.53 vs 8.10+/-2.80% (P=0.068). AI=1. 17+/-0.33 vs 1.06+/-0.23 (P=0.29). In both groups ACE inhibition and blood pressure response were similar over 24 h and slightly greater 48 h after last dosing. CONCLUSIONS: In renally impaired subjects fosinopril and HCTZ can be coadministered without undue increases in fosinoprilat concentrations or any clinically significant pharmacodynamic effects. This is probably due to the dual excretory pathways for fosinoprilat.     

The influence of diflunisal on the pharmacokinetics of oxazepam.

Single dose pharmacokinetics of oxazepam, 30 mg, have been studied in six healthy male volunteers in the absence of diflunisal and during continuous treatment with diflunisal 500 mg twice daily. During diflunisal treatment, peak plasma concentration of oxazepam significantly decreased from 387 +/- 18 ng ml-1 (mean +/- s.e. mean) to 241 +/- 10 ng ml-1 and total area under the plasma concentration-time curve (AUC) significantly decreased from 5536 +/- 819 ng ml-1 h to 4643 +/- 562 ng ml-1 h. The AUC of oxazepam glucuronide significantly increased from 4771 +/- 227 ng ml-1 h to 8116 +/- 644 ng ml-1 h and its elimination half-life increased from 10.0 +/- 0.6 h to 13.0 +/- 1.0 h. Renal clearance for oxazepam glucuronide was significantly reduced from 74 +/- 2 ml min-1 to 46 +/- 3 ml min-1. In vitro, diflunisal, at concentrations of 125 to 1000 micrograms ml-1, significantly displaced oxazepam from its plasma protein binding, the free fraction of oxazepam increasing by 28 to 56%. The free fraction of oxazepam glucuronide, ex vivo, increased by 49 +/- 5% (n = 3) during concomitant diflunisal treatment. These data suggest that the observed interaction between oxazepam and diflunisal results from a presystemic displacement of oxazepam from its plasma protein binding sites by diflunisal and from an inhibition of the tubular secretion of oxazepam glucuronide by the glucuronides of diflunisal.     

Determination of yohimbine in serum by high performance liquid chromatography

An automated method for determination of yohimbine (Yoh) in the serum was developed by means of column switching high performance liquid chromatography (HPLC). TSK-precolumn BSA-ODS and TSK-gel ODS-120T were used as a precolumn and analytical column, respectively. The wavelengths of detection were used at 280 nm (excitation) and 360 nm (emission). A 100 microliter serum sample is directly injected onto the precolumn. Yoh is then eluted within 30 min with an methanol-potassium phosphate buffer mixture. The analytical recoveries (99.3-110.4%), reproducibilities (within-run, C.V. less than 2.27%), and detection limit (0.80 ng/ml, S/N = 3) indicate that this system is suited for determination of Yoh. The five healthy volunteers received a single oral dose 10 mg of HYoh powder. The average of the maximal serum concentration and the area under the curve (AUC) from 0 to 4 h were 10.3 +/- 0.88 ng/ml and 19.70 +/- 0.87 ng.h.ml-1, respectively. The elimination rate constant (Kc1) was 0.52 +/- 0.03 h, and biological half-life (t1/2el) was 1.32 +/- 0.12 h.     

The disposition of amodiaquine in man after oral administration.

A method is described for the simultaneous determination of amodiaquine (AQ) and desethylamodiaquine (AQm) in plasma, urine, whole blood and packed red cells. After oral administration of AQ (600 mg) to seven healthy subjects, absorption of AQ was rapid, reaching peak concentrations in plasma, whole blood, and packed cells at 0.5 +/- 0.03, 0.5 +/- 0.1 and 0.5 +/- 0.1 h respectively (mean +/- s.e. mean). The apparent terminal half-life of AQ was 5.2 +/- 1.7 h. AQ was detectable for no longer than 8 h. AQ underwent rapid conversion to AQm, which reached peak concentrations in plasma, whole blood and packed cells at 3.4 +/- 0.8, 2.3 +/- 0.5 and 3.6 +/- 1.1 h respectively. AQm was still detectable at the end of the sampling period (96 h) when the plasma concentration was 29 +/- 8 ng ml-1. The area under the plasma concentration vs time curve (AUC(0, infinity] for AQ was 154 +/- 38 ng ml-1 h; the corresponding value for AQm was 8037 +/- 1383 ng ml-1 h. There were no significant differences in the values for AUC of AQ between plasma, whole blood, or packed cells. The whole blood to plasma concentration ratio for AQm was 3.1 +/- 0.2, and the AUC (0.24) for AQm in whole blood (6811 +/- 752 ng ml-1 h) was significantly greater than that in plasma (2304 +/- 371 ng ml-1 h), P less than 0.001. The recovery of AQm from urine collected 0-24 h was 6.8 +/- 0.8 mg (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)     

气相色谱法测定人血浆中非洛地平浓度及药代动力学

采用气相色谱—电子捕获检测法测定人血浆中非洛地平浓度,研究中国男性正常人口服该药的药代动力学规律,为临床用药提供依据。血浆样品经乙醚—正己烷(2∶1)萃取浓缩后进行测定。结果表明非洛地平浓度在0.5～10ng·ml^-1范围内线性良好(γ=0.9991)。此法简便易行,精密度好,日内、日间的RSD分别小于5.09%及8.62%。回收率平均为97.3%±4.0%。测定了10名健康者单次口服非洛地平10mg后不同时间的血药浓度并计算了相应的药代动力学参数。     

Clinical pharmacokinetics of the nifedipine/co-dergocrine combination in impaired liver and renal function.

Following a single oral dose of 20 mg nifedipine combined with 2 mg co-dergocrine to 24 subjects, the pharmacokinetics of this drug were studied. 8 normotensive subjects had normal renal and hepatic function, 8 patients had chronic renal insufficiency (creatinine clearance less than 30 ml.min-1) and 8 patients had liver cirrhosis which was confirmed by liver biopsy. The area under the plasma level time curve (AUC infinity) of co-dergocrine increased from 0.59 +/- 0.41 ng.ml-1. (mean +/- SD) in the normals to 1.24 +/- 0.95 ng.ml-1.h in liver cirrhosis (P less than 0.05) and to 1.81 +/- 0.9 ng.ml-1.h in renal failure (P less than 0.05 compared with the control group). Corresponding values for the nifedipine AUC infinity were 564.5 +/- 268 ng.ml-1.h, 1547.5 +/- 1134 (P less than 0.05) and 929 +/- 533 ng.ml-1.h (P less than 0.05; gas chromatographic method). The incidence of adverse effects was lower in patients with renal failure than in subjects with normal renal and liver function as well as in those with liver cirrhosis.