防治血吸虫病药物的研究 ⅩⅩⅪ.酒石酸锑树脂的制备及试验治疗

弱碱性阴离子交换树脂,能与吐酒石的阴离子结合,形成酒石酸锑树脂.口服时可减轻胃肠道反应,吸收缓慢而均匀.家犬一次给药后,血锑高峯约在9-24小时间,多次给药后基础血锑浓度可达1.0-3.5微克/10毫升全血.血吸虫病犬经用酒石酸锑树脂治疗二周后,减虫率达86％以上.     

防治血吸虫病药物的研究 ⅩⅩⅪ.酒石酸锑树脂的制备及试验治疗

弱碱性阴离子交换树脂,能与吐酒石的阴离子结合,形成酒石酸锑树脂.口服时可减轻胃肠道反应,吸收缓慢而均匀.家犬一次给药后,血锑高峯约在9-24小时间,多次给药后基础血锑浓度可达1.0-3.5微克/10毫升全血.血吸虫病犬经用酒石酸锑树脂治疗二周后,减虫率达86%以上.     

~3H-莪术醇在正常大鼠及肿瘤小鼠体内的代谢研究

~8H-莪术醇自大鼠胃肠道吸收迅速且完全。灌胃后5分钟血中即有放射性,15分钟达高峰,1小时仍保持较高浓度,放射性自血中消失的生物半衰期为11.5小时(t_(1/2)β)。静脉注射后血中放射性的消失分快、慢两相,生物半衰期分别为33分钟(t_(1/2)α)及12.5小时(t_(1/2)β)。 放射性在正常大鼠体内分布情况与肿瘤小鼠者相似。肝及肾组织含量约为其它组织的2～2.5倍。肿瘤组织中的分布与其它组织无明显差别;组织中放射性的消失与血浆中者略呈平行关系。放射性与脂肪组织似有较强的亲和力,给药后4小时仍维持较高水平。 放射性主要自尿排泄,口服或静脉注射后24小时分别自大鼠尿排出剂量的45.38％及51.91％。胆汁为另一排泄途径,大鼠口服或静脉注射后24小时,分别自胆汁排出36.47％及56.43％,而口服或静脉注射后72小时仅从粪回收6.77％及14.35％,可见,自胆汁排出的放射性大部分均又被重吸收入血。     

3H-莪术醇在正常大鼠及肿瘤小鼠体内的代谢研究

³H-莪术醇自大鼠胃肠道吸收迅速且完全。灌胃后5分钟血中即有放射性,15分钟达高峰,1小时仍保持较高浓度,放射性自血中消失的生物半衰期为11.5小时(t_(1/2)β)。静脉注射后血中放射性的消失分快、慢两相,生物半衰期分别为33分钟(t_(1/2)α)及12.5小时(t_(1/2)β)。放射性在正常大鼠体内分布情况与肿瘤小鼠者相似。肝及肾组织含量约为其它组织的2～2.5倍。肿瘤组织中的分布与其它组织无明显差别;组织中放射性的消失与血浆中者略呈平行关系。放射性与脂肪组织似有较强的亲和力,给药后4小时仍维持较高水平。放射性主要自尿排泄,口服或静脉注射后24小时分别自大鼠尿排出剂量的45.38%及51.91%。胆汁为另一排泄途径,大鼠口服或静脉注射后24小时,分别自胆汁排出36.47%及56.43%,而口服或静脉注射后72小时仅从粪回收6.77%及14.35%,可见,自胆汁排出的放射性大部分均又被重吸收入血。     

薄层紫外扫描法测定五味子醇甲在大鼠体内的代谢及脑内分布

五味子醇甲为五味子乙醇提取物中有效成分之一,具有明显中枢安定作用,本文用薄层紫外扫描方法测定醇甲在大鼠及小鼠体内的吸收、分布、排泄及脑内分布。大鼠口服醇甲后,胃肠吸收快,静注后血药浓度呈开放二室模型。组织分布以肺浓度最高,其次为肝、心、脑、肾、肠、脾及肠最低。脑内分布以下丘脑、纹体、海马浓度最高,其次为低位脑干及间脑,大脑皮层和小脑浓度较低。静注后由尿排出量很少。醇甲自整体小鼠的消失快。结果表明醇甲自胃肠道吸收快而完全,代谢及排泄较快,组织分布广。各脑区药物浓度的差别可能与其中枢作用有关。     

正常人发锑、尿锑和血锑的测定

我院于1976年测定了我矿区内87名无锑接触史正常人的发锑、尿锑及46名正常人血锑含量数值,现将结果报告如下: 采样方法:87例一并留发和留尿供检测。男性全理发,女性剪项发和余发,以2～3克为限。留24小时尿。46例正常人血锑的检测方法是空腹于肘静脉注抽血5毫升。测定方法:取平行样品,发锑、尿锑所测含量误差小于20％的范围。按玫瑰精B法作定量分析。取样品先用硝酸、硫酸和高氯酸使有机物破坏,然后在7一gN盐酸酸度中用二氯化锡还原锑为三价,加氧化剂亚硝酸钠,新生态的五价锑在高浓度的盐酸中转变为SbCI石,尿素破坏过量的亚硝酸钠后,在4一SN盐酸酸度中,SbC此与玫瑰精B的正离子作用,生成离子络合物,用苯萃取后,经72型分光光度计比色测定。     

薄层紫外扫描法测定五味子醇甲在大鼠体内的代谢及脑内分布

五味子醇甲为五味子乙醇提取物中有效成分之一,具有明显中枢安定作用,本文用薄层紫外扫描方法测定醇甲在大鼠及小鼠体内的吸收、分布、排泄及脑内分布。 大鼠口服醇甲后,胃肠吸收快,静注后血药浓度呈开放二室模型。组织分布以肺浓度最高,其次为肝、心、脑、肾、肠、脾及肠最低。脑内分布以下丘脑、纹体、海马浓度最高,其次为低位脑干及间脑,大脑皮层和小脑浓度较低。静注后由尿排出量很少。醇甲自整体小鼠的消失快。结果表明醇甲自胃肠道吸收快而完全,代谢及排泄较快,组织分布广。各脑区药物浓度的差别可能与其中枢作用有关。     

丙谷胺的临床应用

<正> 丙谷胺即二丙谷酰胺(Proglumide),化学名DL-4-苯甲酰胺-N,N-二正丙基戊酰胺酸,是一种胃泌素受体拮抗剂,用以治疗消化性溃疡。 口服丙谷胺后在胃肠道吸收迅速、完全。如与碱性药物同服,并不影响其吸收。口服2小时血中浓度达高峰,应用治疗量时其最小有效血浓度为2μg/ml。吸收后主要分布于肝、肾和胃肠道,血浆半衰期约为33小时。最后由肠道及肾脏排出。反复应用未见蓄积性毒性作用。     

口服人丹型酒石酸锑钾肠溶丸治疗血吸虫病181例总结

在治疗血吸虫病中,到目前为止,仍沿用着酒石酸锑钾静脉注射法。由于这种给药方法须用大量的人力、物力、财力,就给开展消灭血吸虫病的广大群众运动带来一些不便之处。因此,近年来除继续寻找新药外,对酒石酸锑钾给药方法也在不断进行改革,希望能通过口服方法或其他方法,达到与静脉注射法相同之效果。所以,从五八年以来,我们进行了口服酒石酸锑钾肠溶丸,盐酸奎宁锑等药的临床试验,可是因反应大,疗效不高而没有推广。今年初,按中央血研会布置,我们又进行了人丹型酒石酸锑钾肠溶丸     

硫辛酸对酒石酸锑钾解毒作用的研究

本文研究了国产硫辛酸对酒石酸锑钾的解毒作用.结果证明硫辛酸对酒石酸锑钾的急性及亚急性毒性均有非常显著的解毒作用.小白鼠腹腔注射酒石酸锑钾后,立即以130毫克/公斤的硫辛酸灌胃或皮下注射,可分别使酒石酸锑钾的急性LD₅₀提高1.6和1.9倍.在急性试验中,酒石酸锑钾为LD₉₅时,2-3分子硫辛酸可对抗1分子酒石酸锑钾;在亚急性试验中,酒石酸锑钾为LD₅₀时,1分子硫辛酸即可对抗1分子酒石酸锑钾.腹腔注射酒石酸锑钾LD₅₀后3小时皮下注射硫辛酸,可完全保护小白鼠免于死亡.硫辛酸性质稳定,口服吸收良好,在锑剂中毒出现症状后仍然有效,值得在临床试用.     

三尖杉酯碱的代谢

本文报告³H-三尖杉酯碱在正常及肿瘤鼠体内的吸收、分布和排泄。静脉注射³H-三尖杉酯碱后,大鼠血中放射性迅速降低,快、慢两相的生物半衰期分别为3.5分钟和50分钟。给大鼠静脉注射³H-三尖杉酯硷,注射后15分钟时,药物在各组织中的分布以肾脏为最高,肝、骨髓、肺、心脏、胃肠、脾、肌肉次之,睾丸、血及脑较低。两小时后各组织中的药物浓度均迅速下降,但骨髓的下降较慢,在所有组织中药物浓度居于首位。24小时后则在所测组织中药物浓度均降到相当低的水平。³H-三尖杉酯碱在肿瘤小鼠体内的分布情况与正常大鼠的分布趋势大致相仿。³H-三尖杉酯碱在静脉注射后24小时自大鼠体内排出的总放射性,在尿相当于注射剂量的30.2%,在粪相当于16.6%,其中原型药共占14.5%。此外胆汁也是一条重要排泄途径。静脉注射后24小时可自胆汁排出剂量的24.5%,其中原型药占17.1%。该硷口服给药可迅速吸收入血,但吸收不完全。     

高三尖杉酯碱在大鼠及小鼠的代谢

本文报告³H-高三尖杉酯碱在正常大鼠、小鼠和荷瘤小鼠体内的吸收、分布和排泄。给大鼠静注后,t_1/2(α)和(β)分别为2.1和53.7分钟。静注后15分钟,以骨髓、肾和肝的放射性最高。荷瘤小鼠体内的放射性分布情况与正常大鼠的趋势相仿。静注后24小时,自大鼠尿排泄剂量的42.2%,在粪中排出6.3%,其中原形药放射性占剂量的15.9%。静注后48小时,自胆汁排泄剂量的57.7%,其中原形药放射性占剂量的20.2%。该碱经肌注也可被迅速吸收入血。     

~3H-乙炔雌二醇环戊醚的吸收、分布和排泄

给雌大鼠口服氚标记的乙炔雌二醇环戊醚(EECPE)后半小时血液中即可测出放射性,但10小时后才达高峰。在胃肠道的生物半衰期为13小时,说明~3H-EECPE的吸收较慢。猴服~3H-EECPE后1小时血液即可测出放射性,4小时达高峰。~3H-EECPE被吸收后,在大鼠和猴体内的分布均以脂肪组织的浓度最高,脑组织的浓度也较高,而在靶器官—子宫、输卵管、乳腺—的浓度却不高。~3H-EECPE在各组织中均有较长时间的储留,尤其在脂肪组织中储留的时间更长,这可以解释其口服后的长效作用。~3H-EECPE的主要排泄途径为粪,自尿排出较少。由于在体内储留,所以排泄缓慢。     

雷公藤甲素在大鼠体内过程的研究

雷公藤甲素具有抗肿瘤、抗炎和免疫抑制作用,能迅速由胃肠道吸收,但并不完全。本实验研究了该药口服和静注给药途径的分布和排泄,结果表明:口服和静注后,药物在体内的分布和消除速率大体相似,均以肝中浓度为最高,依次为脾、肺、肾、肠、心和脑,体内消除较缓慢。血浆蛋白结合率为64.7%。24d内,口服后尿粪总排泄量为给药量的67.5% ,其中粪占52.4%;静注后为61.9%,粪占25%。24h内胆汁排泄为6.73%。提取尿、粪和胆汁经TLC、放射性测定及放射自显影分析,表明以原药排泄为主和部分代谢物。     

3H-天麻素在大鼠体内的吸收、分布、代谢和排泄

大鼠口服³H-天麻素后,胃肠道放射性消失很快,8h仅剩给药后即刻放射性的1.1%。口服后5min血中放射性已有较高水平,50min左右达高峰。静注或口服后,组织放射性均以肾最高。肝、肺、子宫其次。脑中放射性较低,但变化不同于其他组织,2h达高峰。天麻素血浆蛋白结合率为4.3%,其甙元(对羟基苯甲醇)为69.3%。天麻素在体内主要代谢物是甙元。口服后放射性主要从尿排泄。口服后24h内从尿、粪和胆汁排出的总放射性分别为剂量的66.1,0.63和3.06%.     

瑞香素的代谢及药代动力学

本文报告用紫外分光光度法测定生物样品中瑞香素的方法,并用该法研究了瑞香素在大鼠体内的药代动力学。所得血药浓度—时间数据依一定程序在709电子计算机上拟合曲线,并计算有关参数。体外实验证明瑞香素可被血及肝、肾、肺等组织所代谢,且可与血浆、肝及肾组织蛋白结合。又将瑞香素以静脉注射和灌胃两种途径给药后直接观察在大鼠体内的组织分布和在尿粪胆汁中的排泄,结果表明本药分布广,主要经肾排泄,且排泄较快。     

3H-乙炔雌二醇环戊醚的吸收、分布和排泄

给雌大鼠口服氚标记的乙炔雌二醇环戊醚(EECPE)后半小时血液中即可测出放射性,但10小时后才达高峰。在胃肠道的生物半衰期为13小时,说明³H-EECPE的吸收较慢。猴服³H-EECPE后1小时血液即可测出放射性,4小时达高峰。³H-EECPE被吸收后,在大鼠和猴体内的分布均以脂肪组织的浓度最高,脑组织的浓度也较高,而在靶器官—子宫、输卵管、乳腺—的浓度却不高。³H-EECPE在各组织中均有较长时间的储留,尤其在脂肪组织中储留的时间更长,这可以解释其口服后的长效作用。³H-EECPE的主要排泄途径为粪,自尿排出较少。由于在体内储留,所以排泄缓慢。     

Paraquat disposition in rats, guinea pigs and monkeys

LD50 doses of ¹⁴C-labeled paraquat were administered to rats, guinea pigs and monkeys by gavage, and radioactivity was determined in excreta and tissues. Rat urine was analyzed for paraquat metabolites by thin-layer chromatography. [¹⁴C]Paraquat was absorbed from the gastrointestinal tract and reached highest serum values 0.5–1 hr after administration. Disappearance of [¹⁴C]paraquat from serum was characterized by a rapid initial decline followed by a prolonged slow decline. Tissue paraquat values were higher than serum values in rats and guinea pigs. Relative to other tissues, paraquat accumulated transiently in the lung and reached peak concentration 32 hr after administration. In rats a major portion of administered paraquat was not absorbed from the gastrointestinal tract. At 32 hr after paraquat, 52% of the administered dose remained in the gastrointestinal tract and 17 and 14% of the administered dose was excreted in the feces and urine, respectively. No radioactivity was recovered in expired air or flatus. Excretion of paraquat in urine and feces was prolonged in all species. In monkeys paraquat was measured in urine and feces 21 days after administration. Chromatography of urine from [¹⁴C]paraquat-treated rats revealed no metabolites. The primary pathologic changes induced by paraquat in the lung may be related to the transient uptake of the chemical by that organ.     

INTESTINAL HANDLING OF MERCURY IN THE RAT: IMPLICATIONS OF INTESTINAL SECRETION OF INORGANIC MERCURY FOLLOWING BILIARY LIGATION OR CANNULATION

Three sets of experiments were carried out to determine if there is an intestinal secretory component in the fecal excretion of administered inorganic mercury. In the first set of experiments the disposition of a nontoxic 0.5-mumol/kg intravenous dose of inorganic mercury was evaluated in control rats and rats whose bile duct had been ligated. Data collected 24 h after the administration of mercuric chloride indicated that some inorganic mercury had moved from the blood across the epithelium into the lumen of the stomach, small intestine, and large intestine. This secretory movement of mercury was most prominent in the small intestine. Interestingly, the renal uptake and accumulation of mercury were diminished significantly in the rats whose bile duct had been ligated. A time-course experiment showed that the maximum amount of secretory movement of mercury into the lumen of the small intestine occurred during the initial 12 h after the injection of mercuric chloride. By the end of 24 h after the injection of mercuric chloride, much of the inorganic mercury secreted in the small intestine appeared to have moved down into the large intestine. In a third experiment, the disposition of mercury was evaluated in control rats and rats who had their bile duct cannulated. The rationale for this third experiment was to study the disposition of mercury under conditions where obstruction of biliary outflow from the liver would not be as much of an issue as with ligation of the bile duct. Evidence for movement of mercury into the lumen of the intestines was also obtained from the rats whose bile duct had been ligated. Eighteen hours after the injection of mercuric chloride the amount of mercury in the luminal compartment of the small intestine was not statistically different between the two groups of rats. Approximately 1.7-2.1% of the administered dose was present in the luminal contents of the small intestine. Decreased renal uptake of mercury was also detected in the rats whose bile duct had been cannulated. The findings from the present study show that when bile flow is obstructed or diverted, clear evidence for secretory movement of mercury into the lumen of the gastrointestinal (GI) tract can be demonstrated. These findings also indicate that the secretory movement of mercury into the lumen of the GI tract is a mechanism that contributes significantly to the pool of mercury that is excreted in the feces.     

Studies of metabolic fate of a new antiallergic agent, azelastine (4-(p-chlorobenzyl)-2-[N-methylperhydroazepinyl-(4)]-1-(2H)-phthalazinone hydrochloride)

The metabolic fate of a new antiallergic agent, azelastine (4-(p-chlorobenzyl)-2-[N-methylperhydroazepinyl-(4)]-1-(2H)-phthalazinone hydrochloride) in rats and guinea pigs was investigated using its 14C-labelled compound. The blood level of radioactivity reached the maximum at 1-1.5 hr after oral administration, indicating the rapid absorption of the drug from gastrointestinal tract. A high concentration of radioactivity was detected in the lung of both species following either oral or intravenous administration. The major pathway of excretion of radioactivity was by way into feces, in both species. The radioactivity excreted in feces was attributable to that which was excreted in bile and exsorbed into gastrointegtinal tract. When the drug was given to pregnant rats, the concentration of radioactivity in the fetus was significantly lower than those in placenta and uterus, indicating the limited placental transfer of the drug. The successive oral administration of the drug in lower doses exerted no effect on the activity of microsomal drug-metabolizing enzymes of rat liver, while in higher doses, had a slight effect.