摘要:

AbstractThe effect of various antidiuretic drugs was studied in rats with lithium‐induced polyuria. Constant polyuria (urine volume>150 ml/24 hrs, Uosm<200 mosmol/kg) was induced in male Wistar rats by administration of LiCl in the food for 2–3 months before the experiments. Body weight, food consumption and urine volume and osmolality were recorded daily. After a 7 days control period, drugs were administered once or twice daily for 7 days. Bendroflumethiazide, 0.4, 2 and 10 mg/kg daily orally, produced a reversible, dose‐dependent antidiuretic response as indicated by a decrease in free water clearance. After 10 mg/kg, negative free water clearance was induced and the urine flow was reduced to one third. Diazoxide, chlorpropamide and carbamazepine did not significantly affect urine volume or osmolality at dose levels producing no effects on food consumption or body weight. The antidiuretic response to a thiazide diuretic and the lack of response to drugs known to have antidiuretic action in pituitary diabetes insipidus, lend support for the nephrogenic basis of the concentration defect induced by li

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03101.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractFormulae are presented for multicompartment modelling of drug binding to plasma proteins based on non‐linear saturation kinetics. Two‐ and three‐compartment solutions are described in more detail. The data concerning warfarin binding to rat plasma proteins fitted well to a three‐compartment model indicating two binding sites. The amount of free drug increased from 4 % at low concentration (less than 10 μg/ml) to 39 % at the highest concentration (500 μg/ml). The mean extravascular extracellular protein concentration and the size of extracellular space of the rat was calculated with constants obtained from the literature, and a curve was constructed describing the theoretical warfarin binding in extravascular extracellular space. The binding percentages of two binding systems for warfarin were calculated by means of graphic analysis for both plasma and interstitial fluid proteins. The percentage of the second binding system was greater than that of the first system at high total drug concentrations. The second binding system also had a more prominent role in the extravascular space than in plasma even at relatively low total warfarin concentrations. The present approach may provide a useful and practical way of calculating drug binding to extracellular

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03102.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe elimination of trimethoprim and sulphadoxine after intravenous administration has been investigated in experiments on goats. Trimethoprim is metabolized to a great extent in the goat liver and the biliary excretion was almost equal to the urinary excretion in experiments with continuous intravenous infusion of trimethoprim. More than 99 % of the amount excreted in bile consists of metabolites of trimethoprim. In contrast it was almost exclusively the unchanged drug which was excreted in the saliva. Sulphadoxine is metabolized to a much smaller extent in goats than trimethoprim and the biliary and salivary excretion seemed without significance in comparison to the urinary excretion.

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03103.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe half‐life of trimethoprim is about 40 min. in adult goats and 4–5 times longer in newborn kids. During the neonatal period the half‐life decreases to the level found in adult goats when the body weight is about 10 kg corresponding to an age of 40–50 days. The half‐life of sulphadoxine is about 12 hours in adult goats and there is a tendency towards a longer half‐life in newborn and young kids, but the difference is not significant. The apparent volume of distribution for both trimethoprim and sulphadoxine is higher in newborn kids than in adult animals. The apparent volume of distribution for trimethoprim decreases during the neonatal period while that of sulphadoxine is nearly constant until an age

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03104.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe ratio between the maximum iodine concentrations obtained in the urine during osmotic diuresis after intravenous injection of the contrast media metrizamide, sodium iocarmate and sodium diatrizoate, should theoretically be 6:4:3. To confirm this, the renal excretion of the three media and the main urinary solutes was investigated in rabbits with a catheter in both ureters. The contrast media were injected in iodine‐equivalent amounts at two dose levels, both relevant for urographic examinations. Urine samples were collected within the first hour after the injection. Blood pressure was also recorded. After low solute loading the excretion of potassium was depressed. A positive linear correlation was found between the excretion rates of potassium and sodium and all data fitted the same line regardless of the contrast medium. After injection of the sodium salts the sodium recovery was less than the corresponding iodine recovery at low solute loading and greater at the highest solute loading. Free water reabsorption was not related to the contrast medium. The ratio between the maximum iodine concentrations in the urine after injection of the high dose of the contrast media was found to be 148:120:7

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03105.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe soluble proteins from two samples of normal human liver were subjected to gel filtration. Zinc, cadmium, mercury, copper, arsenic, and selenium were determined in each molecular weight fraction by neutron activation analysis. The results are presented as “protein‐trace element spect

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03106.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractEffects on critical flicker fusion frequency (CFFF), coordination and mood were studied after single oral doses of placebo, alcohol (0.5 ml ethanol/kg b. wt.), oxazepam (10, 20 and 40 mg), diazepam (5, 10, 20 and 40 mg) and methylperone (10, 25 and 50 mg), given either alone, or simultaneously with alcohol or with delayed alcohol administration. Methylperone was found to have a depressant effect similar to or greater (on a weight basis) than that of diazepam and oxazepam respectively. The correlation between sedative and antianxiety effect is discussed. The decrease in CFFF was parallelled by a decreased coordination ability. Alcohol alone had no effect on our parameters, but when given simultaneously with the drugs, it markedly increased the effect of diazepam, while the effect of oxazepam and methylperone were affected to a much lesser degree. The effect of the drugs on psychomotor skills and the interaction between alcohol and the drugs have important implications when treating out‐patients. Methylperone as a potential anti‐anxiety agent is discus

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03107.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

摘要:

AbstractThe toxicity of d‐amphetamine was greater than that of 1‐amphetamine in adult mice with intraperitoneal dosage range of 10–50 mg/kg. In these doses neither isomer was toxic to developing mice aged 12–16 days. Both isomers of amphetamine induced a dose‐dependent hyperthermia in adults, and the response was stronger after the d‐ than the 1‐form. Ten mg/kg of d‐amphetamine increased the temperature of developing mice, while 50 mg/kg of both isomers was markedly hypothermic; p‐OH‐amphetamine (10 and 50 mg/kg) was not lethal and lacked the thermal effect in adult and developing mice. Phenoxybenzamine (20 mg/kg) completely protected adult mice against the toxicity of 50 mg/kg of d‐amphetamine. It also attenuated the d‐amphetamine‐induced hyperthermia in adult as well as hypothermia in developing mice. Propranolol (10 mg/kg) partially protected adult mice against d‐amphetamine toxicity and clearly antagonized the hyperthermia. In combination with propranolol d‐amphetamine was toxic to developing mice and potentiated the hypothermia. Metoclopramide (40 mg/kg) partially protected adult mice against d‐amphetamine toxicity and diminished the hyperthermia. In developing mice, metoclopramide increased d‐amphetamine toxicity, but decreased the hypothermia. It is suggested that amphetamine preferentially affects noradrenergic mechanisms in adult mice and dopaminergic mechanisms in developing mice. Central noradrenaline receptors seem to be mainly responsible for the mediation of amphetamine toxicity. Amphetamine‐induced disturbances in thermoregulation play a minor role in amphetamine toxicit

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03108.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY

ISSN:0001-6683    

DOI:10.1111/j.1600-0773.1976.tb03109.x

出版商:Blackwell Publishing Ltd    

年代:1976

数据来源: WILEY