Hydrocortisone stability in human feces.

Hydrocortisone stability in human feces was studied under various conditions to determine whether stability accounts for the variable effects of hydrocortisone enemas. Recovery from feces and assay specificity were assured using dual isotopes, TLC separation, and liquid scintillation counting. Hydrocortisone degraded slightly from 7 to 26% in 24 hr when incubated in fresh human feces at 37 degrees. Less than 7% degradation occurred in feces stored at 10 degrees, and negligible degradation occurred with hydrocortisone in water at 37 degrees. Fecal bacteria may account for the observed degradation. Hydrocortisone stability in feces may contribute to local persistence and may account partly for its efficacy in ulcerative colitis treatment.     

Amitriptyline-induced constipation in cynomolgus monkeys is beneficial for the evaluation of laxative efficacy

In an attempt to create an animal model of constipation in monkeys, amitriptyline was administered to cynomolgus monkeys at doses of 10-160 mg/kg body weight via a nasogastric tube. Normal control monkeys excreted feces frequently throughout the day. Monkeys treated with amitriptyline at doses of 10-40 mg/kg showed delays in feces excretion. The 60 mg/kg treated monkeys for the most part did not excrete feces during the 24 h after amitriptyline administration. The 80 and 120 mg/kg treated monkeys did not excrete feces until 24 h from administration of amitriptyline, and also showed prolonged crouching and lethargy. On the other hand, 160 mg/kg treated monkeys died within 24 h after administration. We therefore felt that the optimal dose for creating constipation in the monkeys was 60 mg/kg. We tested the appropriateness of this amitriptyline-induced constipated monkey model by observing the effects of a new laxative, the herbal medicine ND-10 and the commercially available laxative bisacodyl. Control monkeys (those not receiving ND-10 or bisacodyl) treated with 60 mg/kg amitriptyline did not excrete feces up to 32 h after amitriptyline administration in 2 of 3 monkeys. However, all monkeys treated with one tablet of ND-10 excreted feces. Also, in 4 monkeys administrated with bisacodyl, 3 excreted feces. In this study, we confirmed that constipation can be caused in cynomolgus monkeys by oral administration of amitriptyline. This model may also be useful for the evaluation of laxatives.     

Effect of thiamine on the excretion of subcutaneously injected lead in rats

The effect of thiamine on the excretion of lead in feces was investigated using rats injected subcutaneously with lead acetate and thiamine pyrophosphate. The amount of lead excreted increased with the amounts of thiamine administered, while lead concentrations in blood, liver and femur also increased. The amount of lead excreted in feces decreased, however, with administration of oxythiamine and vanadium. These results suggest that excretion of lead in feces is enhanced by thiamine and that it promotes evacuation of lead from the body.     

Use of accelerating solvent extraction for detecting non-steroidal anti-inflammatory drugs in horse feces

Feces are a possible medium to be used for horse doping control. Efficient methods for detecting drugs in feces collected from various animals are routinely applied in institutes of food safety in Belgium. We have already tested whether they are applicable to horse feces. In this report, accelerated solvent extraction (ASE), an efficient method for extracting compounds from solid material, has been tested. ASE has been used to replace the diethyl ether liquid-liquid extraction step present in the method initially set up. This technique has been optimized for detecting several non-steroidal anti-inflammatory drugs (NSAIDs) in horse feces. Extraction recovery and limit of detection have been determined for several NSAIDs, such as meclofenamic acid, flunixin, vedaprofen, celecoxib, carprofen, diclofenac, and ketoprofen. The method has been successfully applied to meclofenamic acid, flunixin, and phenylbutazone post-administration feces samples, and the main metabolites identified in urine were also detected in feces. In the case of meclofenamic acid, the detection profile in feces presented in this report is in accordance with our previous finding in feces obtained with the original method. The use of ASE decreases the time necessary for sample preparation. This method is applicable on a large scale, which is useful for horse doping control.     

Quantitative relationship of fecal asbestos to asbestos exposure.

A method is descirbed for isolating chrysotile fibers from feces and counting them with an electron microscope. The detection limit was 150,000 fibers per gram feces; average recovery was 85.5%. When the method was used to check the asbestos in feces of people subjected to industrial exposure vs. controls, the means were significantly different (p less than 0.02). Duplicate fecal samples were found to check within an average of +/- 31.1% of their means.     

染料木黄酮在Beagle犬体内的药代动力学染料木黄酮在Beagle犬体内的药代动力学

目的研究染料木黄酮(genistein)在Beagle犬体内的药代动力学。方法染料木黄酮ig后用反相高效液相色谱法测定犬血浆、尿及粪便中原型药物浓度,血浆药物浓度-时间数据用3P97药代动力学软件分析。结果Genistein在Beagle犬体内的代谢符合一室模型,ig后0.29 h达药峰浓度,t1/2 Ke为0.52 h。给药后24 h内有10.79%的原型药物由尿排出,21.55%的原型药物由粪便排出。60 h内有13.00%的原型药物由尿排出,有52.46%的原型药物由粪便排出。结论Beagle犬ig染料木黄酮后吸收迅速,血浆中药物的消除速度快,药物主要以原型经尿和粪便排出体外。     

Chlordecone metabolism in the pig

The biotransformation of chlordecone (CD) to chlordecone alcohol (CDOH) occurs in man and gerbils but not in rats, guinea pigs and hamsters [1, 2]. Because of the species differences in CDOH formation and the need for a suitable animal model, pigs were administered CD by intraperitoneal (i.p.) injection. Plasma, gallbladder bile, hepatic bile, liver and feces were collected and analyzed by gas chromatography for CD metabolites. CDOH was present in bile and feces with up to 85% conjugated in the bile but only 15% was conjugated in the feces. Up to 20% of the CD in plasma and bile and less than 3% in feces was in the conjugated form. Both reduction and conjugation of CD in the pig are similar to those in man.     

金双歧对肠易激幼鼠肠道菌群影响的研究

目的通过金双歧治疗肠易激幼鼠模型观察金双歧对幼鼠肠道菌群的影响。方法建立幼鼠肠易激模型,共20只,随机选同期正常生长幼鼠10只为正常组A,另取肠易激模型幼鼠10只为模型组B,取10只用金双歧治疗为实验组C。然后对三组幼鼠分别作粪便含水量检测及肠道菌群检测。结果小鼠建立肠易激模型后肠杆菌、肠球菌数量明显增多（P〈0.05）,双歧杆菌、乳酸杆菌数量大量减少（P〈0.05）：用金双歧治疗10d后,肠杆菌、肠球菌数量减少（P〈0.05）,双歧杆菌、乳酸杆菌大量增多（P〈0.05）,3组鼠粪便干湿重及粪便含水量比较,B组与A、C组间有显著差异（P〈0.05）。结论金双歧治疗肠易激综合症对幼鼠粪便性状症状及肠道菌群有明显改善,为应用益生菌治疗肠易激综合症提供理论依据。     

合生元对小鼠便秘及肠推进作用的研究

目的研究合生元对小鼠便秘及肠推进作用的影响。方法将昆明雄性小鼠随机分为正常对照组、模型对照组和4个剂量的给药组,给药组分别经口给予不同浓度的合生元(1、3、5、10 g.kg-1)0.2 mL.(10 g·d)-1空白组和模型组给予0.2 mL.(10 g·d)-1的生理盐水。用复方地芬诺酯制造小鼠便秘模型,建模后各组分别给药,观察各组小鼠的首次排黑便时间、5 h内排便粒数、粪便质量和小肠墨汁推进率。结果合生元给药15 d,可明显改善便秘小鼠首次排黑便时间、增加排黑便粒数和质量;同时可显著提高便秘小鼠小肠墨汁推进率。结论表明该合生元具有润肠通便功能。     

静脉注射不同内酯型比例的羟基喜树碱后原形药物经小鼠尿液和粪便排泄的研究

目的:研究静脉注射不同内酯型比例的羟基喜树碱(HCPT)后原形药物经小鼠尿液、粪便的排泄情况。方法:静脉注射不同内酯型比例(100%,75%,50%,25%,0%)的HCPT溶液。分别收集给药后0~3,3~6,6~9,9~12,12~24,24~48 h的尿液和粪便样品,测定其中原形药的含量。结果:原形药从尿液中的累积排泄量分别为12.81%,20.00%,27.01%,32.75%,41.04%,从粪便中的累积排泄量分别为13.91%,18.58%,24.44%,27.48%,31.30%。结论:小鼠尿液和粪便中HCPT原形药物的累积排泄量与HCPT内酯型比例呈负相关,这可能与药物的极性有关。给药后3 h内药物以尿液排泄为主,3~12 h主要从粪便中排泄,12 h后极少从尿液和粪便中排泄。     

Elimination of products of fluoracizine by the gastrointestinal tract in animals of different species]

A study on elimination of phthoracizine metabolites with feces of different animal species evidenced that bulk of its transformation products with an intact side-chain was contained in the feces of rats. In the feces of mice they are found in much smaller amount, while in rabbits they are practically untracable. The phthoracizine transformation products devoid of the side-chain are demonstrable both in rats and in other animal species either as traces or not definable at all. These phenomena are, apparently, to be attributed to a different ability of eliminating the phthoracizine biotransformation products with bile by different animal species, which, among other factors. is determined by the molecular weight of individual metabolites.     

Metabolic disposition and pharmacokinetics of [14C]-amprenavir, a human immunodeficiency virus type 1 (HIV-1) protease inhibitor, administered as a single oral dose to healthy male subjects

The objective of this study was to determine the metabolic profile, routes of elimination, and total recovery of amprenavir and its metabolites after a single oral dose of [14C]-amprenavir. Six healthy male subjects each received a single oral 630 mg dose of amprenavir containing 95.76 microCi of [14C]-amprenavir in this Phase I mass balance study. The metabolic disposition of amprenavir was determined through analyses of radiocarbon in whole blood, plasma, urine, and stool samples, collected for a period of 10 to 17 days postdosing. Cerebral spinal fluid (CSF) sampling was conducted on day 1. The ratio of unchanged amprenavir AUC0-->infinity to plasma radiocarbon was 27%, suggesting that most of the radiocarbon was metabolites. The median total recovery of the administered dose of radiocarbon was 89% (range: 66%-93%), with 75% (range: 56%-80%) recovered in the feces and 14% (range: 10%-17%) in the urine. Most of the recovered radiocarbon in the feces and urine was excreted within 240 and 48 hours postdose, respectively. Of the 75% of the radiocarbon dose recovered in the feces, 62% was identified as a metabolite resulting from dioxidation of the tetrahydrofuran ring (GW549445X) and 32% as a metabolite resulting from subsequent oxidation of the p-aniline sulfonate group (GW549444X). Unchanged amprenavir was below the limit of quantitation in feces and urine. Therefore, approximately 94% of the dose excreted in the feces was accounted for by these two metabolites. Concentrations of radiocarbon in the CSF were below the limit of quantitation in 5 of 6 subjects sampled. In summary, oral amprenavir is extensively metabolized in humans, with concentrations of unchanged drug below the limits of quantitation in urine and feces. The majority (75%) of administered radiocarbon was excreted in feces.     

7-乙基-10-羟基喜树碱脂质体在大鼠体内的代谢和排泄

目的考察7-乙基-10-羟基喜树碱(SN-38)脂质体经静脉注射后,在大鼠尿液、粪便中的代谢产物以及以SN-38原形药物排泄的量。方法大鼠尾静脉单次给予2.77 mg/kg SN-38脂质体,分别于0～6、6～12、12～24、24～48 h分段收集尿液、粪便,采用UPLC/Q-TOFMS法对SN-38脂质体在大鼠尿液、粪便中的代谢产物进行鉴定,并且建立HPLC法,用于大鼠尿液及粪便样品中SN-38原形药物的排泄量的测定。结果 SN-38脂质体的在大鼠体内的代谢产物经鉴定为SN-38G。48 h内脂质体组共有1.57%的原形药物经过尿液排出,共有12.94%的SN-38原形药物经过粪便排出。结论 SN-38脂质体只有少部分以原形药物经尿液和粪便排出体外。     

Elimination pathways of [14C]losoxantrone in four cancer patients.

Losoxantrone is an anthrapyrazole derivative in Phase III development in the U.S. for solid tumors, notably breast cancer. To obtain information on the routes of elimination of the drug, a study was conducted in four patients with advanced solid tumors, which involved intravenous administration of 100 microCi of [14C]losoxantrone for a total dose of 50 mg/m(2) during the first course of losoxantrone therapy. Blood, urine, and feces were collected for up to 2 weeks and were analyzed for total radioactivity and parent drug. In addition, feces were profiled for the presence of metabolites. Plasma concentrations of total radioactivity exhibited a temporal pattern similar to the parent drug. Combined recovery of administered total radioactivity from urine and feces was 70% with the majority (87%) of this radioactivity excreted in the feces, presumably via biliary excretion. Feces extracts were profiled for metabolites using a high-performance liquid chromatography method developed to separate synthetic standards of previously identified human urinary metabolites. Only intact losoxantrone was found in the feces. About 9% of the dose was excreted in the urine, primarily during the first 24 h and mostly in the form of parent compound. Collectively, these data indicate that fecal excretion of unmetabolized drug via biliary and/or intestinal excretion is the primary pathway of intravenously administered losoxantrone elimination in cancer patients with refractory solid tumors.     

Metabolic disposition of 14C-metanil yellow in guinea pigs.

The absorption, metabolism and excretion of 14C-metanil yellow was studied in guinea pigs. Following administration of a single po dose of 5 mg dye (7.6 mu Ci)/kg body weight, 83.4% was excreted through urine and feces within 96 h with the majority accounted for in feces. Liver, kidney and spleen did not have marked accumulation of counts, whereas testes and gastrointestinal tract retained 1.9 and 9.7% of the radioactivity, respectively. Analysis of urine and feces detected 2 azo-reduction metabolites of metanil yellow which were characterized by TLC and IR, NMR and mass spectroscopic studies as metanilic acid and p-aminodiphenylamine.     

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。     

普罗布考促进小鼠体内胆固醇逆转运的研究

目的检测普罗布考干预后小鼠血清脂质,血清、肝脏及粪便中3H-胆固醇占经腹腔注射3H-胆固醇总量的百分比,探讨普罗布考对小鼠体内胆固醇逆转运的影响。方法32只C57BL/6小鼠随机分为4组,给予不同剂量普罗布考(0,0.1%,0.5%,1%W/W)添加饲料饲养4wk后,腹腔注射经ac-LDL及3H-胆固醇处理过的RAW264.7小鼠巨噬细胞悬液(0.5ml/鼠,细胞数达5.0×106,放射活性达6.2×106cpm),单笼喂养24h后取血,酶法测定血清脂质;收集血清、肝组织、0～24h粪便,分别用液闪计数仪测定3H-胆固醇含量(均以占注射总量百分比计);结果0.1%普罗布考干预4wk后总胆固醇(TC)较对照组降低34.3%,52.8%,(P<0.01),低密度脂蛋白胆固醇(LDL-C)及甘油三酯(TG)降低20%,22%,(P<0.05);0.5%和1%普罗布考降低TC,HDL-C47%,55%,(P<0.01);降低LDL-C和TG为32%,30%,(P<0.05)。腹腔注射巨噬细胞悬液24h后血清中3H-胆固醇含量呈剂量依赖性轻度降低,而肝脏和粪便中3H-胆固醇含量呈剂量依赖性明显升高,分别为20%～48%(P<0.05)和20%～84%(P<0.01)。结论普罗布考虽然降低HDL-C血浆水平,但是明显促进胆固醇的逆转运,加速了胆固醇经粪便的清除,利于动脉粥样硬化的防治。     

Pharmacokinetic and metabolic studies of vinpocetine on dogs. II. Metabolism

Metabolic studies of vinpocetine were carried out by analysing the excreta of dogs treated orally or intravenously with the labelled compound. Our studies including various extraction procedures, TLC and MS structure identification revealed that vinpocetine underwent rapid and extensive metabolism in the animal organism. Unchanged parent drug was excreted via urine and feces only in a small or negligible portion. The prevailing metabolite in both urine and feces was apovincaminic acid. Two minor metabolites were also identified: hydroxy-vinpocetine and dihydroxy-apovincaminic acid-glycine amide. Beside the chemical structures and relative abundances of metabolites found in dogs, qualitative data referring to the metabolites occurring in the feces of orally treated humans, are also presented.     

UPLC-Q-TOF/MS analysis of naringin and naringenin and its metabolites in rat urine and feces after intragastric administration of alcohol extract of Exocarpium Citri grandis

To analyze naringin, naringenin and its metabolites in rat urine and feces after intragastric administration of alcohol extract of Exocarpium Citri Grandis, healthy SD rats were fed with alcohol extract of Exocarpium Citri Grandis for 3 days. On the last day, 0-24 h feces and 0-4 h, 4-8 h, 8-24 h urine were collected and analyzed by UPLC-Q-TOF/MS. The post-acquisition data were processed using Metabolynx The result is that naringin and its 6 metabolites, naringenin and its 4 metabolites were detected in the urine of rat. Meanwhile, naringin and its 3 metabolites, naringenin and its 2 metabolites were detected in the feces of rat.     

Kinetics of the excretion of a membrane-active macroheterocycle from the body in mice

The study of the excretion kinetics of N-(3H-aminoacetyl)-I-aza-4,7,10,13-tetraoxacyclopentadecane hydrochloride and its metabolites with the mouse urine and feces showed a high relative effectiveness of the urinary excretion (only some 2% of the dose is excreted with the feces). It was also found that there occurs an intensive biotransformation of the compound yielding free and water-soluble metabolites.