大黄素及其代谢产物在小鼠体内排泄的定量分析

小鼠口服单剂量大黄素(91mg/kg),在0-48h内,总蒽醌衍生物由尿及粪排泄量为剂量的53%,其中在0-24h内由尿中排出者为30%,由粪中排出者为21%。在24-48h内由尿和粪中排出者为2%。在0-24h内由尿中排出大黄素、大黄素葡萄糖醛酸苷及其它蒽醌类代谢产物的剂量百分数为7.6、1.8和20,粪中分别为13,0.3和8。在24h内由尿中排出的主要游离型代谢转化产物为3-羟甲基-1,6,8-三羟基葱醌(剂量的11.8%),3-羧基-1,6,8-三羟基蒽醌(1.8%),大黄酚(1%)和大黄素甲醚(<1%)。代谢产物的分离鉴定主要采用紫外吸收光谱,薄层层析,高效液相色谱等方法。     

铊在大鼠体内的吸收,分布和排泄

以碳酸亚铊１０ｍｇ／ｋｇ经口给大鼠灌胃染毒，，５分钟后，可在大部份组织中测到铊，半小时，除胃以外，肝中含量最高；１小时后，除胃以外，脾和肾中含量最高，次为心和睾丸；２小时肾中浓度居首位，其高峰期在４－８小时，４小时后，骨中含量增高，仅次于胃，脑，肌肉。     

Effect of nafenopin (SU-13, 437) on liver function

Summary Administration of nafenopin (SU-13-437) to male rats for two days leads to a doubling of bile production and a 50% increase in liver weight. These two effects have been shown not to be directly interrelated. A marked decrease in biliary bile salt concentration suggests that the bile salt independent flow is stimulated. The extra bile produced is probably of canalicular origin since bile to plasma concentration ratios of erythritol are unchanged. At least three polar metabolites of nafenopin have been observed in rat bile. Obervations in rats with partial biliary fistulas indicate that the drug and its metabolites undergo extensive enterohepatic circulation. Our studies support the view that much of the enhanced bile flow is associated with the presence of nafenopin and/or its metabolites within the hepatobiliary system. However, the response is too extensive to be explained merely by osmotic choleresis. Induced structural changes in the liver may also account for some of this effect.This research was supported by U.S. Public Health Service Grant CA 14231 from the National Cancer Institute     

Pantothenic acid status of free living adolescent and young adults

The objective of the current study was to compare estimated dietary pantothenic acid of adolescent and adult humans on self-selected diets with urinary excretion and blood levels of pantothenic acid in order to gain insights on apparent pantothenic acid nutritional status of these individuals. In Study I, 11 adolescent boys and girls ranging in age from 10–16 years participated. Subjects were interviewed on past dietary practices. During the 4-day test period, subjects kept daily records of food intakes and made complete collections of urine. Fasting blood samples were drawn at the end of the study. Study II was similar to Study I except that 23 adult subjects participated. Pantothenic acid contents of urine and blood serum from both studies were determined microbiologically using Lactobacillusplantarum. Intakes of pantothenic acid were calculated from dietary diaries and from the check forms. For adolescent subjects, a strong, statistically significant correlation between pantothenic acid intake and blood serum pantothenic acid was found. However, no statistically significant positive correlation was found between pantothenic acid intake and either pantothenic acid excretion expressed in terms of mg/day or mg/g creatinine. In the latter case, the correlation was directionally negative. For adults, a strong, statistically significant positive correlation was found between pantothenic acid intake and urinary pantothenic acid excretion. However, the relationship between pantothenic acid intake and blood serum pantothenic acid was not statistically significant.     

[~3H]十一酸睾丸素肌注后在大鼠的吸收、分布和排泄

大鼠肌注[~3H]十一酸睾丸素油剂,血浆放射峰在药后2d 出现,32d和60d 的血浆放射性分别为峰值的13.3%及9.9%,放射性的分布以肝、肾、脂肪为高,次为提肛肌、附睾、睾丸、前列腺与储精囊。药后60d,肌注部位残留放射性为给药量的19.9%;尿和粪中放射性累积排泄量分别为给药量的41.4%和9.3%。算得 t_((1/2)ka)=6.9d;t_((1/2)α)=6.9d;t_((1/2)β)=15.4d。     

Effect of α-hexachlorocyclohexane on metabolism and excretion of pentetrazol (Cardiazol®) in the rat

Summary -Hexachlorocyclohexan (-HCH) has been shown to be a potent anticonvulsant when tested with pentetrazol. In the experiments reported here the question was examined whether or not the anticonvulsant properties of -HCH are based on an acceleration of pentetrazol breakdown in the rat.In this study the rat has been shown to metabolize pentetrazol extensively. The enzymatic activity is located in the microsomal fraction of the liver and requires NADPH and oxygen. It is inhibited by SKF-525 A and carbon monoxide. This is taken as evidence that P-450 containing mixed function oxidases are involved in the breakdown of pentetrazol.-HCH pretreatment leads to an acceleration of pentetrazol break-down by microsome preparations of about 140%. In vivo -HCH pretreated rats eliminate pentetrazol from brain and serum with a half life of 1.3 h, while this is 3.8 h in untreated rats.The earliest point in time at which -HCH pretreatment causes diminished brain levels of pentetrazol has been found 60 min after pentetrazol injection. Prior to this brain levels of pentetrazol were identically in untreated and -HCH-treated rats.As pentetrazol elicits convulsions within the first 30 min following oral or subcutaneous administration of a convulsive dose and -HCH is clearly active as an anticonvulsant under these conditions, the accelerated breakdown of pentetrazol cannot be the cause of the anticonvulsive action of -HCH.Supported by Deutsche Forschungsgemeinschaft.H. W. V. was the holder of a grant from Deutsche Forschungsgemeinschaft.     

Effect of cyanide antidotes on the metabolic conversion of cyanide to thiocyanate

The excretion of thiocyanate following the administration of equitoxic doses of cyanide to unprotected mice and to animals pretreated with various cyanide antidotes has been studied.The results demonstrate that cyanide given alone or to animals pretreated with thiosulfate is extensively converted to thiocyanate. Animals pretreated with sodium nitrite or a combination of nitrite and sodium thiosulfate excreted even higher amounts of thiocyanate. This demonstrates that cyanide originally detoxified by combination with methemoglobin is ultimately converted to thiocyanate in the animal body.Pretreatment of animals with cobalt compounds (cobaltous chloride or dicobalt-EDTA) or a combination of cobalt compounds and thiosulfate resulted, on the other hand, in a less efficient conversion of cyanide to thiocyanate. The cyanide detoxified by trapping as highly undissociated cobalt-cyanide complexes is instead excreted in the urine, as demonstrated by detection of high amounts of cobalt ions and strongly complex-bound cyanide in the urine from animals treated with cobalt compounds and cyanide. A method for the determination of cyanide present as cobalt-cyanide complexes is described and its forensic application is proposed.     

Biliary excretion of chlorthalidone in humans

A single oral dose of the diuretic chlorthalidone (100 or 200 mg) was given to six cholecystectomized patients with T-tube drainage of the common bile duct, and the 24 h bile and urine were collected during 3–7 days. Urinary recovery of chlorthalidone was 23–27 per cent of the dose, which is in the range of that in healthy volunteers. Chlorthalidone concentration in bile was 11–44 times lower than urine concentration in corresponding periods, and biliary recovery was only 0·6–1·4 per cent of the dose. When compared from equal periods of sampling of bile and urine, the same relative amount of drug was found in bile, whether the 100 or 200 mg dose had been given (viz., a fraction of 2·5–4·7 per cent and 2·5–5·7 per cent of corresponding urinary amounts respectively). It was concluded that excretion into bile constitutes only a minor route of elimination for unchanged chlorthalidone. Bile samples treated with glucuronidase and sulphatase showed no increase of chlorthalidone concentration. The open acid analogue of chlorthalidone, 3-(4-chloro-3-sulphamoylbenzoyl)-benzoic acid, was apparently not formed as a human metabolite, as evidenced by gas chromatographic analysis of both urine and bile.     

Toxicological properties of surfactants

Surfactants are of considerable importance in the field of detergents and in cosmetics. Of the anionic, nonionic, and cationic surfactants the most important products — as far as sales volume is concerned — belong to the anionic type. Anionic and nonionic surfactants taken orally are of low toxicity according to acute toxicity tests as well as long term studies, while certain cationics are moderately toxic. In local application, compatibility with skin and mucous membranes is strongly dependent on concentration. Surfactant action on biological systems can largely be explained on the basis of physico-chemical properties of the surfactants. Some surfactants show pharmacological activity.     

Effects of Guanosine on the Pharmacokinetics of Acriflavine in Rats Following the Administration of a 1:1 Mixture of Acriflavine and Guanosine,a Potential Antitumor Agent

Preclinical studies are currently underway to examine the potential antitumor effects of a 1:1 mixture of acriflavine (ACF; CAS 8063-24-9) and guanosine. Guanosine potentiates the anticancer activity of some compounds. However, the effects of guanosine on the pharmacokinetics of ACF in mammals are unknown. Therefore, this study investigated the effects of guanosine on the pharmacokinetics of ACF after administering a 1:1 mixture of ACF and guanosine in rats. The rats were given either 10 mg/kg of the mixture or 5 mg/kg ACF via an intravenous bolus injection; or 30 mg/kg of the mixture or 15 mg/kg ACF intramuscularly. An HPLC-based method, which was validated in this laboratory, was used to analyze the levels of trypaflavine (TRF) and proflavine (PRF) in the plasma, bile, urine, and tissue homogenates. It was found that TRF and PRF were rapidly cleared from the blood and transferred to the tissues after the i.v. bolus or i.m. injection of the combination mixture. Both TRF and PRF were found to be most highly concentrated in the kidneys after the i.v. bolus or i.m. injection, followed by slow excretion to the bile or urine. Guanosine had no effect on the plasma disappearance of TRF or PRF after the i.v. bolus injection. However, guanosine led to a prolongation of the plasma levels of PRF after the i.m. administration of the combination mixture, resulting in a 2 fold increase in the bioavailability (BA) of PRF The concentrations of TRF and PRF in all the tissues examined were similar in the groups given the mixture and ACF. However, guanosine led to a prolongation of the biliary and urinary excretions of both TRF and PRF after the i.v. bolus (1.25 fold) or i.m. (1.5-2.4 folds) injection. These prolonged effects of guanosine on the plasma disappearance or urinary excretion of TRF and PRF might be one reason for the enhanced antitumor effects of ACF. However, more study will be needed to further examine this potential mechanism.