~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。     

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%.     

葛根有效成分的代谢研究——Ⅱ.14C-黄豆甙元在大鼠体内的吸收、分布和消除

本文采用纸片液体闪烁计数法研究了¹⁴C-黄豆甙元在大鼠体内的吸收、分布和消除。大鼠口服¹⁴C-黄豆甙元30分钟,血液即可测出放射性,6～8小时达高峰,以后缓慢下降。口服给药吸收不完全,由实验推论约有64.6%放射性可被吸收。静脉注射后,血放射性消失曲线分为快、慢两个时相,其生物半衰期分别为13分钟和42分钟。放射性在肾、肝含量最高,血浆、肺、心次之,肌肉、脾、睾丸、脑较低。静脉注射后,¹⁴C主要自尿排出(24小时可排出剂量的71.2%),自粪排出17.4%。口服后24小时可自尿排出34.3%,自粪排出33.1%。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47.4%;口服后相应时间内排出39.1%。本文所得结果与前文应用化学方法所得结果进行比较,表明自消化道、尿、胆汁所回收的放射性主要是黄豆甙元的代谢产物,说明该药在体内的代谢很旺盛。     

14C-棉酚在四种动物体内吸收、分布和排泄的比较研究

本文比较研究了¹⁴C-棉酚在小鼠、大鼠、犬和猴体内的吸收、分布和排泄过程。小鼠和大鼠于单次口服¹⁴C-棉酚后6～9小时,血内放射性达高峰,生物半衰期分别为31和16.5小时。口服¹⁴C-棉酚48小时后,以胃肠道内容物及肝、肾内放射性最高。睾丸内放射性大鼠比小鼠要高。进入体内¹⁴C-棉酚,放射性排出主要通过粪便,少部分从尿排出。以犬和猴(各1只)进行比较研究,也获得类似结果。它们睾丸内放射性均比大鼠低。与其它三种动物比较,犬心脏内放射性最高,猴体内放射性从粪便中排出最快。本文结果提示棉酚对不同动物的抗生育作用与毒性作用之间的差异,可能与它在相应脏器内的分布、蓄积及排泄速度的不同有关。     

靛玉红及其乙基和十八烷基衍生物在动物体内命运的比较

N₁′-乙基靛玉红(79002)对动物移植性肿瘤的抗癌活性优于靛玉红;而N₁′-十八烷基靛玉红(79005)则较靛玉红差。本文比较了³H-靛玉红及³H-79002和³H-79005在小鼠及大鼠的体内命运。结果表明,³H-79002吸收最易,瘤内放射性最高,组织内存留时间较长;而³H-79005吸收最难,给药后以胃肠分布的放射性最高,组织内存留时间最短。这些结果表明三者体内过程的差别与其抗癌活性的差别相一致。     

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。     

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。     

14C-汉防己甲素双碘甲烷季铵盐在小白鼠体内的代谢

小白鼠皮下注射6 mg/kg ¹⁴C-汉防己甲素双碘甲烷季铵盐后2分钟,放射性在血、肝、肾、腹肌、膈肌、心、肺、脾、尿、胆囊等均有分布,以胆、尿、肝中放射性最强。脑中放射性在90分钟内一直接近本底。血、腹肌、肾、膈肌、肺、脾中的¹⁴C含量均在20分钟达高峰。胆、尿、肝中含量不断升高,到实验终了时(90分钟)为最高。尿中排泄速度以注射后10分钟为高峰。90分钟内尿中排泄¹⁴C占注射量的13%。     

3H-丙硫咪唑在大鼠、小鼠体内分布的研究

本文研究了。³H-丙硫咪唑在大鼠血液和小鼠组织中的分布，结果表 明：丙硫咪唑与一般苯骈咪唑类药有显著不同，易自胃肠道吸收、且能通过血脑屏 障。大鼠血液中放射性在给药后15分钟即能测出，6小时左右达峰值，24小时则绝 大部分已排出。小鼠组织中分布浓度以肝、胃、肾为最高，大脑、小脑等也有一定 数量的分布。放射性排泄主要通过大、小便，尤以泌尿系为主     

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。     

Pharmacokinetic properties of the antimuscarinic drug [3H]-hexahydro-sila-difenidol in the rat

Summary The pharmacokinetics of tritiated hexahydrosila-difenidol ([³H]-HHSiD) were examined in rats. Furthermore, the distribution of radioactivity was studied by means of whole body autoradiography.After i. v. administration of 2.9 mg/kg HHSiD plus [³H]-HHSiD to anaesthetized rats bearing a catheter implanted in the ductus choledochus and receiving a mannitol infusion, HHSiD was rapidly distributed and metabolized. Only 5% of the radioactivity was recovered in blood after 23 s and 0.4% after 2.5 h. 64% of the plasma radioactivity could be extracted with hexane from the samples taken 23 s after administration. 52% of the radioactivity was eliminated within 2.5 h, 13% by urinary and 39% by biliary excretion.Following oral administration of 8.6 mg/kg HHSiD plus [³H]-HHSiD there was an absorption of approximately one fourth of the administered radioactivity within 4 h. By means of whole body autoradiography (i. v. injection) as well as by tissue distribution measurement the highest levels of radioactivity were found in bile, urine, lung, kidney, adrenals, liver and pancreas. Thus, after i. v. administration to rats HHSiD is rather quickly distributed, metabolized and excreted. This explains its low antimuscarinic potency in vivo.Send offprint requests to E. Mutschler at the above address     

10-羟基癸烯酸在动物体内吸收、分布、代谢和排泄

10-癸基癸烯酸(即10-HDA,定位标记为³H-10HDA),经小鼠和大鼠口服后,胃肠道吸收快,峰时均在1h,全身分布迅速广泛,与组织亲和力强,肝中放射性为最高,依次为肾、胰、脂肪、脑、脾、心和肺。平均Vd为9.71/kg。Ig和iv的T1/2β在12.6～22.7h。体内消除较缓慢,31 d内,尿粪中放射性累计排泄分别为给药量的85.4%和13.5%,提取尿和胆汁经分析结果主要以原形药物排出。血浆蛋白结合率为63%。血中放射—性时间曲线符合开放二室模型。     

Comparative evaluation of absorption,distribution, and excretion of YM758, a novel If channel inhibitor,between albino and non-albino rats

1. YM758 is a novel If channel inhibitor for the treatment of stable angina and atrial fibrillation. The absorption, distribution, and excretion of YM758 have been investigated in albino and non-albino rats after a single oral administration of ¹⁴C-YM758 monophosphate.

2. YM758 was well absorbed from all segments of the gastrointestinal tract except for the stomach. After oral administration, the ratio of AUC_{0–1 h} between the plasma concentrations of radioactivity and the unchanged drug was estimated to be 17.7%, which suggests metabolism.

3. The distribution of the radioactivity derived from ¹⁴C-YM758 in tissues was evaluated both in albino and non-albino rats. The radioactivity concentrations in most tissues were higher than those in plasma, which indicates that the radioactivity is well distributed to tissues. Extensive accumulation and slower elimination of radioactivity were noted in the thoracic aorta of albino and non-albino rats as well as in the eyeballs of non-albino rats. The recovery rates of radioactivity in urine and bile after oral dosing to bile duct-cannulated albino rats were 17.8% and 57.3%, respectively.

4. These results suggest that YM758 was extensively absorbed, subjected to metabolism, and excreted mainly into the bile after oral administration to rats, and extensive accumulation of the unchanged drug and/or metabolites into tissues such as the thoracic aorta and eyeballs was observed.     

Absorption,distribution, metabolism and excretion of gemigliptin,a novel dipeptidyl peptidase IV inhibitor,in rats

Abstract

1.?The absorption, distribution, metabolism and excretion of a novel dipeptidyl peptidase IV inhibitor, gemigliptin, were examined following single oral administration of ¹⁴C-labeled gemigliptin to rats.

2.?The ¹⁴C-labeled gemigliptin was rapidly absorbed after oral administration, and its bioavailability was 95.2% (by total radioactivity). Distribution to specific tissues other than the digestive organs was not observed. Within 7 days after oral administration, 43.6% of the administered dose was excreted via urine and 41.2% was excreted via feces. Biliary excretion of the radioactivity was about 17.7% for the first 24?h. After oral administration of gemigliptin to rats, the in vivo metabolism of gemigliptin was investigated with bile, urine, feces, plasma and liver samples.

3.?The major metabolic pathway was hydroxylation, and the major circulating metabolites were a dehydrated metabolite (LC15-0516) and hydroxylated metabolites (LC15-0635 and LC15-0636).     

联苯双酯的吸收、分布、代谢和排泄

用高效液相层析和放射性同位素法研究了联苯双酯在大、小鼠体内的代谢及人的排泄。联苯双酯口服后吸收缓慢而不完全;静脉给药后t1/2β为5.78小时,分布容积较大,且易向脂肪组织转移。动物和人经口给药后,原形药物的70%左右自粪排出。自尿和胆汁排出者均为其代谢产物。体外温孵证明,联苯双酯可被肝脏迅速代谢。灌胃给药后用HPLC法很难测到血浆和组织中的药物,提示药物吸收后被迅速转化,可能存在明显的首过作用。     

Studies on the toxicology of hexachlorobenzene I. Pharmacokinetics

In female rats dosed orally with ¹⁴C-hexachlorobenzene the extent of intestinal absorption of carbon-14 has been found to be dependent on the form of application. When the substance was given as a solution in oil about 80% of the dose administered was absorbed, but when given as an aqueous suspension only 6%.In animals treated with ¹⁴C-hexachlorobenzene dissolved in oil, all tissues contained radioactivity. Highest levels were found in adipose tissue, lowest in blood and muscle. Peak values of radioactivity were reached between 2 to 5 days after application.Elimination was studied after intraperitoneal application of 4 mg/kg ¹⁴C-hexachlorobenzene dissolved in oil. Two weeks after administration, 34% of the radioactivity administered was recovered in the feces and 5% in urine. About 80% of carbon-14 excreted in feces and about 4% in urine was contained in the unchanged drug. This indicates that biodegradation of hexachlorobenzene in the rat is not insignificant. No radioactivity was detected in the expired air.The authors are indebted to Prof. J. Portig for many helpful suggestions. Miss A. Springer gave valuable technical assistance.