呋喃丙胺体内代谢的研究

本文利用比色法测定了家兔门静脉血液及心脏血内呋喃丙胺(F30066)的含量.应用光谱分析,纸层析及柱层析法研究了宿主肠道内及尿内呋喃丙胺代谢产物.采用实验治疗血吸虫病的方法,比较胃肠道外不同给药途径的治疗效果.家兔口服呋喃丙胺经胃肠道吸收后,在门静脉血液内有一定浓度的药物.此药经过肝脏转化后部分排泄入肠道.此肠内转化物无治疗血吸虫病的效用.口服呋喃丙胺后尿内可发现二个药物的代谢产物.经体内、体外试验此二代谢产物,均无杀死血吸虫的作用.静脉、肌肉注射呋喃丙胺混悬液治疗血吸虫病家兔都无疗效.腹腔注射呋喃丙胺治疗小白鼠血吸虫病却获得良好效果.     

呋喃丙胺-C~(14)体内吸收、分布和排泄的研究

呋喃丙胺(下称F-30066)是我国发现抗血吸虫病口服非锑类型新药。经动物和临床研究证明,本品对血吸虫病有显著疗效,对其他一些肠道寄生虫也有驱虫作用。 F-30066的药理研究国内已有不少报道,临床和动物代谢的研究阐明,服药后F-30066在体内经代谢转化,从血液、胆汁、肠内容物和尿液中均发现有呋喃丙胺代谢产物。肝、     

吐酒石与呋喃丙胺类药物合并应用治疗家兔日本血吸虫病的研究

感染日本血吸虫病的家兔用F30385或呋喃丙胺治疗,剂量分别为50及150毫克/公斤×14天时,无论在结束治疗时或治后4周内,寄居在小肠肠系膜静脉内的血吸虫显著减少或消失,且移行至肝内的两性虫皆退化死亡,但残留在直肠静脉内的虫数则与治前相仿,虫的大小及形态亦无明显变化,若在治疗的第1—2天,于口服F30385或呋喃丙胺前2小时注射6—12毫克/公斤的吐酒石,以促使肠系膜下静脉内的虫体肝移,则不仅可提高减虫率,且可使部分病兔获得治愈。     

用伊文思蓝法观察呋喃丙胺对小白鼠胃的刺激作用及拮抗药的探讨

本文介绍用伊文思蓝法观察呋喃丙胺对小白鼠胃的刺激作用。动物于口服药物后即由尾静脉注入1%伊文思蓝,并于2小时后剖杀取胃,根据胃底浆膜面的蓝色色素沉着情况,评价药物对胃的刺激作用。试验证明,小白鼠一次口服呋喃丙胺或二甲苯后,用伊文思蓝法观察药物对胃的刺激作用与组织病理学的观察结果相仿。这种方法具有操作简便、快速、灵敏和重现性高等优点。在拮抗试验中,发现扑尔敏、异丙嗪、苯海拉明和氯丙嗪具有较强的拮抗呋喃丙胺对鼠胃的刺激作用,抗炎类药物次之,而阿托品则甚差。用伊文思蓝法观察的结果表明,小白鼠每天口服呋喃丙胺500 mg/kg,连续10天时,药物对鼠胃的刺激作用逐渐减轻,至给药10天后,胃的刺激反应仅及第1次给药时的1/3。若在疗程的第1～3天,每天于口服呋喃丙胺前1小时先服扑尔敏,则呋喃丙胺对鼠胃的刺激作用,仅在给药的第三天较明显,但轻于单服呋喃丙胺3天组。用肉眼或组织病理学方法观察胃肠病变的结果,与伊文思蓝法的基本一致。扑尔敏不影响呋喃丙胺的抗血吸虫作用。     

用伊文思蓝法观察呋喃丙胺对小白鼠胃的刺激作用及拮抗药的探讨

本文介绍用伊文思蓝法观察呋喃丙胺对小白鼠胃的刺激作用。动物于口服药物后即由尾静脉注入1％伊文思蓝,并于2小时后剖杀取胃,根据胃底浆膜面的蓝色色素沉着情况,评价药物对胃的刺激作用。试验证明,小白鼠一次口服呋喃丙胺或二甲苯后,用伊文思蓝法观察药物对胃的刺激作用与组织病理学的观察结果相仿。这种方法具有操作简便、快速、灵敏和重现性高等优点。在拮抗试验中,发现扑尔敏、异丙嗪、苯海拉明和氯丙嗪具有较强的拮抗呋喃丙胺对鼠胃的刺激作用,抗炎类药物次之,而阿托品则甚差。用伊文思蓝法观察的结果表明,小白鼠每天口服呋喃丙胺500 mg/kg,连续10天时,药物对鼠胃的刺激作用逐渐减轻,至给药10天后,胃的刺激反应仅及第1次给药时的1/3。若在疗程的第1～3天,每天于口服呋喃丙胺前1小时先服扑尔敏,则呋喃丙胺对鼠胃的刺激作用,仅在给药的第三天较明显,但轻于单服呋喃丙胺3天组。用肉眼或组织病理学方法观察胃肠病变的结果,与伊文思蓝法的基本一致。扑尔敏不影响呋喃丙胺的抗血吸虫作用。     

口服吸附剂氧化淀粉的体外吸附力实验

口服吸附剂氧化淀粉(Oxystarch)又名二醛淀粉,该药能有效地清除病人肠道内的代谢废物氮和氨,增加大便中的排氮量,降低血液中的尿毒素,从而为慢性尿毒症患者提供了一种新的治疗手段。它很有希望成为一种常规辅助性治疗药     

呋喃丙胺和呋喃丙胺加敌百虫肛栓治疗血吸虫病科研工作交流会报道

在中央和上海市有关部门的领导和支持下,呋喃丙胺和呋喃丙胺加敌百虫肛栓治疗血吸虫病科研工作交流会于1973年4月4日～6日在浙江省嘉兴县召开。参加会议的有浙江、安徽、江西、湖南、江苏五个省和上海市的血防科研方面的代表和战斗在血防第一线的广大医务工作者,共71个单位,108名代表。会上上海市呋喃丙胺科研协作组作了工作汇报,上海市寄生虫病研究所和部分临床单位分别作了关于敌百虫直肠给药合并口服呋喃丙胺的药理试验研究和临床应用廿天疗法、呋喃丙胺加敌百虫肛栓的十天疗法等情况交流。经过热烈讨论,到会同志一致认为:呋喃丙胺是我国医药科技工作者在总路线的光辉照耀下,发扬独立自主、自力更生的精神,首创成功的抗     

糖尿病肾病药物治疗体会

糖尿病肾病是糖尿病晚期严重并发症之一,其发病率与病程长和高血压密切相关。因此,在合理饮食控制血糖的基础上,有选择地应用降糖、降压药物是该病治疗的重要组成部分。 在降糖药的选择上,糖适平应列为首选药,因其作用温和,代谢完全,代谢产物95％经胆道系统后,从粪便中排出体外,仅5％的代谢产物在尿中排泄,对肝、肾功能无任何毒副作用,是治疗该病最为理想的药物。成人一般用量:30～120mg/d,分3决于餐前口服。其次,应选用美吡达,它口服安全,奏效快,降糖作用维持时间长,且体内半衰期较短,以失活的代谢产物迅速从尿中排出,故毒副作用甚微。对治疗该病疗效显著,用法用量:每日2.5～20mg,分3次于餐前口服。再次,达美康最宜用于Ⅱ型糖尿病的治疗,也适用于糖尿病肾病的早期治疗。糖尿病患者长期服用此药,对糖尿病肾病的发生可起到重要的预防作用。其用法为,80～160mg/次,1～2次/日。至于优降糖、D_(860)等磺酰脲类药物因主要经肝脏代谢,其代谢产物近50％由肾脏排泄,故不适用于该病的治疗。降糖灵体内吸收后以原型及代谢产物由尿中排出,并可促进糖的无氧酵解,易发生乳酸性酸中毒而     

氟苯氧丙胺

氟苯氧丙胺(Fluoxetine hydrochloride Prozac 20mg,胶囊)是一种批准用于治疗大多数抑郁疾患的新型抗抑郁制剂,它是通过相对地选择阻止中枢神经系统5—羟色胺的吸收而达到抗抑郁作用。氟苯氧丙胺口服吸收好,一次量后血药浓度峰值约在6小时。此药广泛代谢,主要代谢产物为去甲基氟苯氧丙胺,也有对5-羟     

吡喹酮、尼立达唑和呋喃丙胺治疗埃及血吸虫病217例

在毛里塔尼亚,采用随机方法,设四组:分别用吡喹酮、尼立达唑(又名安必拉)、呋喃丙胺和安慰剂(食糖淀粉片)治疗埃及血吸虫病217例。结果表明吡喹酮、尼立达唑和呋喃丙胺均有疗效,其中以吡喹酮和尼立达唑效果为佳,两者疗效相似。但吡喹酮疗程短、服药方法简单,副作用小,呋喃丙胺疗效较差。吡喹酮是治疗埃及血吸虫病较为理想的一种有效药物。     

宿主组织对F-30066抗血吸虫作用的影响

本文研究了宿主组织对F-30066[卽β-(5-硝基-2-呋喃)丙烯酰异丙胺]体外杀虫作用的影响。实验结果表明,F-30066与小白鼠或家兔的脑、肝、小肠、脾及肾等组织匀浆在36—37℃水浴中保温15—120分钟时,药物的杀虫效价明显降低或消失,心及肺等组织对药物杀虫效价的影响较小。此外,小白鼠的肝、小肠切片降低药物效价的速率较其匀浆慢。F-30066与小白鼠或家兔的红血细胞在上述温度中保温较长时间后(4—8小时),药物的杀虫作用亦有不同程度的降低,但人与犬的红血细胞对药物抗血吸虫作用的影响不明显。     

用生物鉴定法观察抗血吸虫新药吡喹酮在家兔体内的吸收、分布和排泄

用以血吸虫为标本的生物鉴定法,观察了抗血吸虫新药吡喹酮在家兔体内的代谢。自家免胃肠道的不同部位注入吡喹酮时,以小肠的吸收最好,直肠次之,而结肠和胃则较差。药物自小肠吸收后,周围静脉血浆的药浓度较门静脉的低10倍以上。家兔口服吡喹酮100mg/kg的血浆药浓度与皮下注射20mg/kg的相仿;肌肉注射吡喹酮20mg/kg的血浆药浓度较皮下注射的为高;若静脉注射相同剂量,则于注射完毕时虽有甚高的血药浓度值,但药物可迅速自血浆中消除。吡喹酮多次给药时无积蓄作用;若每4小时给药一次,连给3次,则可依次增加血浆的药浓度。家兔一次口服吡喹酮30分钟～4小时,以胃、小肠组织的含药量较高,肝、肾和脑等次之。给药后24小时,除胃和小肠外,其余脏器组织中的药物均已消除。此外,自服药兔的粪、尿中检获有生物活性的物质。     

F-30066体外抗血吸虫作用的研究

本文研究了F-30066,即β-(5-硝基-2-呋喃)丙烯酰异丙胺,体外抗血吸虫的作用.实验证明F-30066对体外血吸虫具有直接杀灭作用.在含F-30066 4-10微克/毫升的Tyrode液与绵羊血清混合液(2∶1)内,虫体表现为活动减弱、萎缩、肠管扭曲、生殖器官退化和子宫内虫卵数减少,终至麻痹死亡.经F-30066作用1—4小时的虫体移置于不含药物的培基中时,其活力可明显恢复,经药物作用8—16小时的则较差,至作用24小时后,虫体的活力不能恢复.在药物对宿主体内虫体生活力影响的观察中,发现小白鼠口服F-300661/2 LD₅₀×4—5天后.其体内受作用的虫体活力在培基内不能完全恢复,虫体的生活时间仅及对照组的一半左右.用吐酒石治疗的动物,于投服1/2 LD₅₀×5天后,其体内存活的虫体活力在培基内迅速恢复,虫体的生活时间与对照组的相似.F-30066的体外杀虫作用能被半胱氨酸与谷胱甘肽所拮抗,而胱氨酸、二巰基丁二酸钠、硫辛酸及维生素丙等则无此作用.用口服F-30066半小时到8小时后的家兔血清培养血吸虫时,虫体的生活时间显著缩短.     

Absorption and excretion of suprofen in rats

DL-2-(4-(2-Thienylcarbonyl)phenyl)propionic acid (suprofen, S) was rapidly absorbed in rats after oral administration. Blood levels after a single oral dose of 2, 10, 50, or 100 mg/kg of 3H-S reached maxima within 30 min and were dose-dependent. The major portion of the drug was shown to be absorbed from the upper part of the small intestine and a portion from the stomach. The radioactivity in rat plasma was extensively bound to the plasma protein in vivo; this was found to be unchanged S and four metabolites. Elimination of S and its metabolites from blood was rapid; 3H was mostly excreted in the urine and feces within 24 hr after oral administration of 3H-S. No significant amounts of 14CO2 were excreted in expired air after administration of 14C-S. Rat urine contained S and four metabolites found in rat plasma, accounting for about 60% of the urinary radioactivity. After rats with biliary fistulas were given an oral dose of 2 mg/kg of 3H-S, 41% of the dose was excreted in the bile during 48 hr; there was significant enterohepatic circulation. When single or 21 consecutive daily doses of 3H-S were administered to rats, the blood levels after the multiple doses were higher than those after a single dose but no significant difference was found in excretion of 3H.     

Metabolic disposition of 6-ethyl-3-(1H-tetrazol-5-yl)-chromone, a new antiallergic agent, in the rat, guinea-pig, rabbit, dog and monkey.

1. [14C]Ethyltetrazolylchromone ([14C]ETC) was promptly absorbed from the rat small intestine by the portal route. 2. The maximum plasma concn. of unchanged drug after oral administration (10 mg/kg) was highest in dogs (456 microgram/ml), followed by monkeys (287 microgram/ml), guinea-pigs (146 microgram/ml) and rats (55 microgram/ml), and lowest in rabbits (09 microgram/ml). The half-life of the drug in plasma varied with the species, ranging from 13 to 133 h. The drug was highly bound to plasma protein. In dogs and rats, the plasma 14C was predominantly the unchanged drug, whereas in guinea-pigs, rabbits and monkeys it was mainly metabolites. 3. At 10 min after oral administration of the drug to rats there was a wide distribution of the 14C in the tissues. At this time, the 14C concn. were the highest in stomach, followed by kidney, liver, plasma, heart and lung, and lowest in brain. 4. Almost all administered 14C was eliminated from the body in 72 h. The major route of excretion was via the urine except with guinea-pigs, in which animal the 14C was almost equally divided between urine and faeces. 5. only trace amounts of the unchanged drug were found in urine and bile. The major urinary metabolites were as follows: I (1-hydroxyethyl ETC), II (acetyl ETC), III (IIIa, 2-hydroxyethyl ETC) and IV (1,2-dihydroxyethyl ETC) in rats, I and VI (5-carboxymethylsalicylic acid) in guinea-pigs, I, III (IIIb, carboxymethyl ETC) and VII (ETC-N-1-glucuronide) in rabbits, I and VII in dogs, and I and IV in monkeys.     

抗肿瘤药物的研究——Ⅵ.对-双(2-氯乙基)氨基-隣甲氧基-苯丙氨酸的实验治疗及毒性

肿瘤化学治疗中氮芥类药物占有重要的地位,临床上已证明这类药对某些造血系统肿瘤有一定的疗效.近年来,很多学者都沿着这条路线,继续寻找更理想的药物.自溶肉瘤素(sarcolysin)发现以来,氨基酸类的氮芥更引起了大家的注意.我们茌这方面也进行了较系统的工作,在筛选中发现对-双(2-氯乙基)氨基-邻甲氧基-苯丙氨酸(药物编     

F30385实验治疗血吸虫病的初步研究

实验发现F30385是一个兼具明显杀日本血吸虫童虫与成虫的硝基呋喃丙烯酰胺类的口服药物。小白鼠一次口服F30385的半数致死置为979±98毫克/公斤(P=0.95)。小白鼠感染尾蚴后4-11天,一次口服F30385 11.4毫克/鼠,减虫率高达90-99%,显著比对32天成虫的杀虫作用强。按等毒性剂量用F30385及F30066治疗小白鼠与兔血吸虫病的结果,F30385的疗效比F30066高。7只感染血吸虫病的犬用总剂量为700毫克/公斤的7-14天疗法治疗后,减虫率为95%。动物口服F30385后的毒性反应主要为胃肠道刺激与肾和肝的受损。小白鼠病理观察结果认为,停药后病变均渐恢复。     

F30066对家兔肝肾功能的影响

F30066, N-(isopropyl)-β-(5-nitro-2-furyl)-acrylamide, is a new oral drug for Schis- tosomiasis japonica. The present work studied the effect of F30066 on the liver and kidney functions of uninfected and infected rabbits six weeks after the cercarial infection of Schistosoma japonicum. The experimental results indicate that the drug causes some damages to the liver and the kidney, but the damages are reversible. The authors also observed the normal-value distributions of several useful tests for liver and kidney func- tions in about 200 animal-times of rabbits.     

Pharmacokinetics of theophylline and its metabolites in rabbits

The pharmacokinetics of theophylline (1,3-DMX) and its metabolites were investigated in detail in four male rabbits after bolus intravenous injection (12 mg/kg) of the compound. Theophylline was measured in blood and urine, and its metabolites were determined only in urine. Apparent first-order rate constants for the metabolic processes involved in the formation of 1,3-DMX metabolites and their excretion in urine were calculated. An appropriate 13-compartment model was formulated to describe the disposition of 1,3-DMX and its metabolites.     

The effect of chlorthalidone on blood sugar and glucose tolerance in the rat

Chlorthalidone, in high doses, failed significantly to influence blood sugar or intravenous glucose tolerance in the rat, following the intraperitoneal injection of single doses or 28 day oral treatment with the drug (100 mg/kg daily). The significant effect of the drug in stimulating glucose transfer in everted sacs prepared from rat intestine may explain the trend towards altered oral glucose tolerance observed. Chlorthalidone failed significantly to influence the blood sugar of alloxan diabetic rats and did not modify glucose uptake by rat-hemidiaphragm muscle or epididymal adipose tissue incubated in vitro in the presence or absence of insulin.