培氟沙星药代动力学和体外抗菌活性研究

本文报道培氟沙星体外抗菌活性及药代动力学研究结果。用HPLC法测定血清药物浓度。6名健康志愿者(男女各半)口服400mg培氟沙星后,体内过程符合一室开放模型。血峰浓度于4h达到,为8.20±2.84μg/ml,表观分布容积为3.05L/kg,AUC为163.08μg·h/ml,消除半衰期为13.35h。体外抗菌活性研究表明本品对常见致病菌有较强抗菌活性。对金葡球菌、大肠杆菌、变形杆菌、痢疾杆菌与伤寒杆菌的MIC_(30)(μg/ml)分别为0.25、2、2、0.25和1。上述结果表明,口服400mg培氟沙星后,其血峰浓度远较多种细菌的MIC_(90),预期临床可取得较好结果。     

环丙沙星药代动力学和体外抗菌活性研究

本文报道环丙沙星体外抗菌活性及药代动力学研究结果。用HPLC法测定血清药物浓度。6名健康志愿者环丙沙星400mg口服后,体内过程符合一室开放模型。血峰浓度于2小时到达,为2.52±0.82μg/ml。表现分布容积为2.47L/kg,AUC为14.10μg·h/ml,消除半衰期为2.93小时。体外抗菌活性研究结果表明,本品抗菌谱广,抗菌活性强。对金葡菌、大肠杆菌、肺炎杆菌、痢疾杆菌、伤寒杆菌MIC90分别为0.125、0.5,0.06、<0.03和0.25μg/ml。对绿脓杆菌抑苗率达87％。上述资料表明,环丙沙星口服400mg后,峰浓度明显高于多种细菌的MIC90值,预期临床可取得较好疗效。     

环丙氟哌酸的药效学和毒理学研究

本文研究了环丙氟哌酸的体外抗菌作用、体内保护作用、小鼠和大鼠一次给药的半数致死量和安全试验。结果表明,环丙氟哌酸对革兰氏阴性菌的MIC范围为0.005～0.19μg/ml,抗菌活性强于氟哌酸、氟啶酸和吡哌酸;对革兰氏阳性菌的 MIC为0.045～1.50μg/ml,其抗革兰氏阳性菌活性明显强于上述对照药。小鼠分别感染金葡球菌、大肠杆菌和绿脓杆菌后的半数有效量明显优于氟哌酸、氟啶酸和吡哌酸。小鼠一次给药的半数致死量,口服LD_(50)为2991.52mg/kg; 静脉为223.88mg/kg;肌肉和皮下的LD_(50)分别为831.08mg/kg和1133.42mg/kg. 大鼠口服LD_(50)>5000mg/kg,静脉LD_(50)>200mg/kg;肌肉和皮下分别为>1000mg/kg和>1200mg/kg。狗口服50mg/kg日服三次为期2日和口服100mg/kg日服一次为期7日,未见毒性反应和功能改变,也未见病理组织学变化。     

双氢青蒿素在人的药代动力学及与青蒿素的比较

用放射免疫测定法研究青蒿素和双氢青蒿素在人的药代动力学结果:人口服青蒿素片剂15 mg/kg后1.5 h,血药峰值达0.09μg/ml,MRT为3.27 h,而口服双氢青蒿素仅1.1 mg/kg和2.2mg/kg后1.33 h,血药峰浓度分别为0.13μg/ml和0.71μg/ml,MRT分别为2.36和2.26 h,可见,青蒿素片剂的生物利用度仅为双氢青蒿素的1.62%～10.08%,所以口服宜用双氢青蒿素。直肠给青蒿素栓剂15 mg/kg和双氢青蒿素栓剂8 mg/kg后,血药分别于4.6 h和4.7 h达峰浓度0.04 μg/ml和0.11 μg/ml,MRT分别为6.98 h和6.96 h,可见青蒿素栓剂的生物利用度仅为双氢青蒿素者的29%,作为栓剂也可用双氢青蒿素。     

甲磺酸加替沙星片健康人单剂口服药代动力学

目的研究健康人口服单剂甲磺酸加替沙星片后药代动力学特征,为该药II期临床试验提供依据。方法采用3剂量3周期拉丁方实验设计。9名健康受试者单剂口服甲磺酸加替沙星片100、200、300mg,HPLC法测其血清、尿药物浓度。结果受试者口服甲磺酸加替沙星片后,人体耐受良好,体内过程符合二室开放模型。主要药代动力学参数与给药剂量呈线性关系,tmax为0.5～0.7h,Cmax分别为1.42、2.42、3.25μg/ml,AUC0-∞分别为11.33、21.85、32.32μg·h/ml,V/Fc值为50～80L,t1/2β为8～9h,72h尿药累积回收率约为63.5%。结论甲磺酸加替沙星片口服吸收良好,血峰浓度高,组织分布广,消除半衰期长。200mg每日一次口服用于治疗敏感菌感染。     

HPLC测定西酞普兰人体血药浓度及其药动学研究

目的建立西酞普兰人体内血药浓度的测定方法,并对其进行药代动力学研究.方法采用HPLC,以盐酸普萘洛尔为内标,以Dikma钻石拄 (4.6 mm×250 mm,5 μm,美国)为色谱柱,以乙腈:0.03 mol/L NH4AC 缓冲液(V:V=33:67)为流动相,测定18名男性健康志愿者单剂量口服西酞普兰后的不同时刻血浆浓度,并根据测定结果求算西酞普兰的药代动力学参数.结果 18名健康志愿者口服西酞普兰40 mg后,血浆中的Cmax为( 54.54±7.83)μg/L ,Tmax 为(3.06±0.42 ) h,AUC0～132 为(2351.1±389.9)μg/L·h ,AUC0～∞为(2636.5±444.9)μg/L·h, t1/2为(40.45±8.68)h.结论本方法重现性好,灵敏度高,可用于临床药物动力学研究.     

口服头孢拉定在血透病员中的药物动力学及给药方案

本文报道4倒尿毒症病员进行血透治疗时口服500mg头孢拉定,透析期内病员体内及透析器的药物动力学参数分别为V_B0.11±0.06和1.1±1.5L/kg;CL0.040±0.024和0.16±0.20L/(kg·h);t_(1/2)1.90±0.26和9±5h。5h透析病员体内药量下降64％,透析器可清除41％药物。表明头孢拉定能被透析清除。3例病员血透前口服500mg头孢拉定的血浓峰值为52.91μg/ml,血透后再给500mg补充剂量,在再次给药前血浓值仍有51μg/ml。     

氧氟沙星药物动力学和体外抗菌活性

6名受试者口服氧氟沙星400mg后,药-时曲线符合一室开放模型。T_(max)和C_(max)分别为1.3h和4.4μg/mL,T_((1/2)ka),T_((1/2)ke)分别为0.8和3.7h,C1为0.36L/(h·kg),V_d为1.9 L/kg。该药对革兰阳性或阴性细菌均有高度抗菌活性,对变形杆菌、痢疚杆菌、大肠杆菌、枸橼酸杆菌、伤寒杆菌和金葡菌等的抑菌率均>90％。     

HPLC法同时测定人尿液中三苯双脒代谢物氨脒和乙酰氨脒的浓度

目的:建立同时测定人尿液中三苯双脒代谢物氨脒和乙酰氨脒浓度的方法,并进行其排泄动力学研究。方法:8名健康男性受试者空腹口服三苯双脒肠溶片400 mg,收集服药前及服药后0~2、2~4、4~6、6~8、8~12、12~24、24~36、36~48 h的尿液。尿样经沉淀蛋白并稀释后,以比卡鲁胺为内标,采用高效液相色谱法进样测定,色谱柱为Agilent Zorbax Extend C18(250 mm×4.6 mm,5μm)流动相为乙腈-水-三乙胺(60∶40∶0.2,V/V/V),紫外检测波长为265 nm,流速为0.7 ml/min,进样量为10μl。结果:氨脒和乙酰氨脒尿药浓度分别在0.5~500μg/ml(r=0.996 2)和0.1~200μg/ml(r=0.995 8)范围内线性关系良好,最低定量限分别为0.5、0.1μg/ml,绝对回收率分别为94.78%~95.23%和91.26%~96.99%,相对回收率为98.37%~101.44%和99.26%~102.06%,日内、日间RSD<7%;-20℃冷冻24 h及7 d和反复冻融均稳定,RSD<7%。受试者口服400 mg三苯双脒肠溶片后,氨脒和乙酰氨脒48 h尿累积排泄率分别为(55.84±13.60)%和(14.98±7.65)%,采用DAS 2.0程序计算氨脒和乙酰氨脒半衰期分别为(3.46±0.73)h和(4.21±0.43)h,尿药排泄速率常数分别为(0.21±0.07)h-1和(0.17±0.02)h-1。结论:该方法简单、快速、灵敏、重复性好,可用于健康受试者口服三苯双脒肠溶片后氨脒和乙酰氨脒尿药浓度的测定。     

奥丹西酮在原发性肝癌患者的药物动力学

目的观察奥丹西酮在原发性肝癌患者体内的药物动力学特性。方法8名接受顺铂 5 -氟尿嘧啶化疗的原发性肝癌患者单次和多次口服16mg 奥丹西酮后 ,应用反相高效液相色谱法测定血浆药物浓度 ,并用PKBP -N1程序在计算机上拟合。结果奥丹西酮表现为二房室模型,其单剂量和多剂量口服主要药动学参数分别为 :T1/2β 为4.3±0.5h和5.7±0.7h(P<0.01),Cmax 为42.6±3.8μg/L和49.2±2.3μg/L(P<0.05),Tmax 为1.8±0.2h和1.8±0.1h,AUC0～∞为643.2±84.7μg/h·L和833.4±96.7μg/L·h(P<0.01)。结论原发性肝癌患者多次口服奥丹西酮后与单次口服相比 ,体内有蓄积现象 ,消除能力下降 ,生物利用度升高     

CATECHOLAMINE INACTIVATION IN UTERINE TISSUES: CHANGES IN PREGNANCY IN THE RAT

1. In vitro metabolism of [3H]-(-)-noradrenaline (3H-NA), 0.2 mumol/l, was measured in rat endometrial and myometrial slices at different stages of gestation and compared with that in dioestrous rats. Metabolism of 3H-NA, 0.2 mumol/l, was measured in rat placental slices from day 14 of gestation onwards. 2. 3H-NA was metabolized mainly by deamination in rat myometrium, with [3H]-3,4-dihydroxyphenylethylene glycol, (3H-DOPEG) being the major metabolite. Cocaine, 30 mumol/l, inhibited 3H-DOPEG formation and the amount of 3H-NA remaining in the tissue. O-methylated metabolite formation was unaffected by cocaine. 3. O-methylation and deamination were equally active pathways for metabolizing 3H-NA in rat endometrium. O-methylation to [3H]-normetanephrine (3H-NMN) predominated in the placenta. In both tissues O-methylated metabolite formation was inhibited by 30 mumol/l cocaine. 4. In myometrium, metabolite formation per gram was constant in the first half of pregnancy and was similar to that in dioestrous animals. By day 17 of gestation, however, [3H]-O-methylated deaminated metabolites (3H-OMDA), comprising 3-methoxy, 4-hydroxy-phenylethylene glycol and vanillylmandelic acid, and 3H-NMN formation were less than in dioestrous animals. 5. Endometrial 3H-NMN and 3H-DOPEG formation per gram were higher in rats at day 5 of gestation than in dioestrous rats but metabolite formation per gram declined thereafter to reach values equal to (3H-DOPEG) or less than (3H-OMDA and 3H-NMN) those in dioestrous rats. 6. 3H-NMN and 3H-OMDA formation per gram decreased from day 14 to day 20 of gestation in rat placentae.(ABSTRACT TRUNCATED AT 250 WORDS)     

2005年北京地区海洛因毒品中稀释剂的分析

目的:对2005年收缴的"零包"海洛因毒品中的稀释剂进行分析。方法:准确称取可疑毒品适量,用SKF525做内标,用乙醇配制成1.0mg.kg-1的样品溶液,取1μl进行GC/MS分析。结果:在408份"零包"海洛因毒品中,检测出含有机稀释剂的323份,占79.2%。检测出的有机稀释剂是烟酰胺(231份,占总份数的56.6%)、咖啡因(135份,占总份数的33.1%)、扑热息痛(51份,占总份数的12.5%)、氨基比林(39份,占总份数的9.6%)、茶碱(37份,占总份数的9.1%)、非那西丁(29份,占总份数的7.1%)、脑复康(28份,占总份数的6.9%)、镇静催眠药(10份,占总份数的2.4%)、曲马朵及其它(10份,占总份数的2.4%)。结论:北京地区"零包"海洛因毒品中多数有有机稀释剂,且种类繁多。脑复康是一个新发现的稀释剂。     

PRESENCE OF CHOLINOCEPTORS IN MESENCEPHALIC RAPHE NUCLEI CONCERNED IN THERMOREGULATION IN RABBITS

1. The thermal effects of cholinomimetics and cholinoceptor blocking agents microinjected into mesencephalic nucleus raphe medianus (NRM) were investigated in rabbits to determine the nature and role of these cholinoceptors in thermoregulation. 2. Microinjection of cholinoceptor agonists, carbachol and pilocarpine, into NRM resulted in significant hyperthermia which could be blocked by local pretreatment with chlorisondamine (a nicotinic receptor blocker) as well as by ethybenztropine (a muscarinic receptor blocker). 3. Intracerebroventricular pretreatment with LM 5008 (serotonin reuptake blocker) significantly inhibited the carbachol-induced hyperthermia. 4. Both nicotinic and muscarinic cholinoceptors are present in mesencephalic NRM which may be involved in thermoregulation in rabbits. Activation of these cholinoceptors in NRM results in hyperthermia which seems to be due to an inhibition of a serotonin sensitive hypothalamic heat loss mechanism.     

国产阿克拉霉素A的体内外抗肿瘤作用

国产阿克拉霉素A(aclacinomycin;ACM-A)能明显抑制体外培养小鼠白血病P₃₈₈和人体胃癌SGC-7901细胞的生长。在0.01 μg/ml浓度时能抑制65.4%的克隆形成,ED₅₀为0.0085μg/ml。ACM-A对白血病小鼠有显著治疗作用,延长小鼠生命时间143%,并有半数小鼠获得治疗。对Ehrlich腹水癌和肉瘤-180也有较强的抑制作用,对肉瘤-180的作用与adriamycin相似。ACM-A主要抑制³H-TDR和。H-UR分别参人人体胃癌细胞的DNA和RNA;大剂量时对蛋白质合成也有影响。P₃₈₈细胞实验中证明ACM-A对DNA合成的抑制程度与adriamycin相似,低于daunomycin。     

HAEMODYNAMIC CHANGES IN ACTH-INDUCED HYPERTENSION IN SHEEP

1. ACTH (20 μg/kg per day) produced an elevation in blood pressure associated with an increase in cardiac output in conscious sheep, due in the first 72 h to a rise in heart rate. Stroke volume did not rise until the fourth day of ACTH treatment. 2. Calculated total peripheral resistance did not change. 3. Intravenous administration of acebutolol prior to and during ACTH administration did not modify the rise in blood pressure, but this was associated with a rise in total peripheral resistance. 4. These studies show that while ACTH-induced hypertension is usually associated with increased cardiac output, rather than total peripheral resistance it still occurs, but is associated with a rise in total peripheral resistance if the rise in cardiac output is prevented by /J-adrenoreceptor blockade.     

INCREASE IN HAEMATOCRIT IN BORDERLINE HYPERTENSIVE MEN

1. Haematologic parameters were measured in untreated borderline hypertensive (BHT) men, and weight and age matched with normotensive men to determine whether previously described increased haematocrit (Hct) in established hypertension is evident in borderline hypertension. 2. Haematocrit was significantly increased in BHT men (mean 0.46, s.d. 0.032) compared with normotensive men (mean 0.43, s.d. 0.014) and correlated significantly with mean arterial pressure in this group (r = 0.67, P= 0.036) independent of weight. 3. The correlation of blood pressure with Hct in BHT men supports the concept that increased Hct may contribute to increased blood viscosity and thus to raised arterial pressure.     

反式曲马朵在大鼠肝微粒体O-去甲基代谢中的立体选择性

目的研究反式曲马朵O-去甲基代谢的立体选择性.方法高效毛细管电泳法测定大鼠肝微粒体孵育液中反式曲马朵和O-去甲基曲马朵对映体的浓度,酶促动力学方法研究O-去甲基曲马朵对映体的生成.结果 (-)-O-去甲基曲马朵生成有较大的Vmax;反式曲马朵两对映体间存在相互作用,使(+)-O-去甲基曲马朵生成的Vmax明显减慢;奎宁及奎尼丁对(+)-O-去甲基曲马朵生成的抑制作用较强.结论反式曲马朵O-去甲基代谢有立体选择性,对映体间的相互作用及酶抑制剂使其立体选择性程度加强.     

PLASMA LEVELS OF ATRIAL NATRIURETIC PEPTIDE IN MAN IN PRIMARY ALDOSTERONISM, IN GORDON''S SYNDROME AND IN BARTTER''S SYNDROME

Plasma levels of ANP were measured in normal subjects and in three conditions associated with disturbed volume homeostasis. Levels of ANP were appropriately raised in seven patients with primary aldosteronism, and fell to normal following removal of an aldosterone-producing adenoma in six and dexamethasone treatment in one patient with glucocorticoid-suppressible hyperaldosteronism. The level of ANP in one patient with Gordon's syndrome (a condition associated with plasma volume expansion) was lower than in the patients with primary aldosteronism, both before and after saline infusion. This is consistent with reduced ANP responsiveness in this condition. responsiveness in this condition. Levels of ANP were inappropriately elevated in three patients with Bartter's syndrome (a condition with plasma volume contraction) and rose further during saline infusion. This is consistent with primary hypersecretion of ANP.     

PRESSOR RESPONSIVENESS IN STEROID-INDUCED HYPERTENSION IN MAN

Pressor responsiveness to angiotensin II (AII) and phenylephrine (PE) was examined before and after 5 days of ACTH (1 mg, i.m., daily) or hydrocortisone (200 mg, orally, daily) in six normotensive men. Pulse pressure was higher prior to PE than AII infusion, presumably due to feeding. Systolic blood pressure (SBP) was increased by both ACTH and hydrocortisone treatment, but more by ACTH. There were no significant changes in AII pressor responsiveness with either ACTH or hydrocortisone. ACTH increased pressor responsiveness to PE at 1.35 and 2 micrograms/kg per min, and hydrocortisone at 0.6-2 micrograms/kg per min, with falls in pulse rate at 0.3-0.9 micrograms/kg per min. Changes in pressor responsiveness do not explain ACTH hypertension.