bluuebunny/crossref_metadata_2025_split huggingface dataset:
A four parameter model for oral drug absorption
Authors: Saunders L , Natunen T 
Published: April 2011

Abstract
A method has been developed for assessing absorption parameters from plasma concentration-time results taken over a relatively short time period. In this method, the disposition function is simplified so as to reduce the number of parameters to be evaluated from the five of the two compartment disposition equation to four, and to avoid the requirement for the evaluation of a slow disposition rate constant. The measurements need not therefore be continued over a period long after absorption is complete. A suitable design for kinetic experiments using this method for interpreting the results, is described. A random noise statistical method is proposed for assessing the stability of the calculated parameters.
Effects of animal maturity on smooth muscle and blood pressure responses to prostaglandins E2 and F2α
Authors: Okpako D T 
Published: April 2011

Abstract
The effects of prostaglandins E2 (PGE2) and F2α (PGF2α) on muscle strips from mature and immature rats and guinea-pigs and on rat blood pressure were investigated in the presence of atropine. The colon and stomach strips from immature rats were equally responsive to PGE2 and PGF2α whereas mature colons were significantly more sensitive to PGF2α and mature stomach strips significantly more sensitive to PGE2. On the ileum from immature guinea-pigs the maximum responses to PGE2 and PGF2α were 16 and 8% of the histamine maximum respectively. The corresponding figures on the mature ileum were 86 and 75%. Whereas PGE2 was only twice as active as PGF2α on immature ilea, it was ten times more active than PGF2α on mature muscles. On blood pressure PGF2α and PGE2 were both hypotensive in immature rats whereas PGE2 was hypotensive and PGF2α hypertensive in mature rats. The results suggest that as the animal gets older, receptors for prostaglandins became increasingly differentiated.
Actions of the muscle relaxant chandonium iodide on guinea-pig ileum and vas deferens preparations
Authors: Harvey A L , Paul Dharam , Rodger I W , Singh Harkishan 
Published: April 2011

Abstract
The effects of the newly synthesized neuromuscular blocking agent, chandonium iodide (17a-methyl-3β-pyrrolidino-17a-aza-D-homo-5-androstene dimethiodide) have been investigated on guinea-pig isolated ileum and vas deferens preparations. On the ileum, chandonium (0·1–10·0 μg ml−1; 1·6 × 10−7m–1·;6 × 10−5m) had weak muscarinic receptor blocking action (pA2 is 5·7), but no antihistamine properties at the concentration tested. No evidence for anticholinesterase actions was found. On the vas deferens, chandonium (10·50 μg ml−1; 1·6–8·1 × 10−6 m) potentiated responses to exogenous noradrenaline; responses to electrical stimulation were potentiated only in the presence of 50 μg ml−1 chandonium. No adrenoceptor or adrenergic neuron blockade was found. The results provide evidence that chandonium acts selectively at acetylcholine receptors and that it is more active as a nicotinic receptor antagonist than as a muscarinic receptor antagonist.
A comparative study of the effect of bile salts on the absorption of quinalbarbitone sodium in goldfish
Authors: Marriott Christopher , Kellaway Ian W 
Published: April 2011

Abstract
The goldfish has been used as a model membrane to estimate the absorption of quinalbarbitone sodium by measurement of overturn time. The effect of sodium cholate, sodium deoxycholate, sodium chenodeoxycholate and sodium taurodeoxycholate on the quinalbarbitone-induced overturn time has been investigated and differences in capacity to promote absorption have been demonstrated. These differences could not be attributed to variations in solubility or partitioning of the drug within the membrane by the bile salts or to the relative hydrophobicity of each molecule. It is suggested that the bile salts must in someway affect the integrity of the goldfish membrane rendering it more permeable to quinalbarbitone sodium.
Changes in crystallinity and solubility on comminution of digoxin and observations on spironolactone and oestradiol
Authors: Florence A T , Salole E G 
Published: April 2011

Abstract
Using infrared spectroscopy, X-ray diffractometry, differential thermal analysis, scanning electron microscopy, solubility and dissolution rate measurements, it was demonstrated that the comminution of digoxin results in the appearance of an amorphous phase. The examination of spironolactone and 17β-oestradiol by infrared spectroscopy and differential thermal analysis showed that these compounds also undergo changes in their crystallinity on grinding. Since the dissolution characteristics of poorly soluble drugs may be complex functions of surface area and crystallinity, it is concluded that the most pertinent method for standardizing a sample of a polymorphic drug of low solubility is by means of a powder dissolution test, as the results embrace the influences of particle size, aggregation and polymorphism.
The effects of administering N-(2-benzoyloxyethyl) norfenfluramine to rats on the hepatic synthesis of glycerolipids
Authors: Brindley David N , Bowley Mariana , Burditt Susan , Pritchard P Haydn , Lloyd-Davies Katherine A , Boucrot Philippe 
Published: April 2011

Abstract
N-(2-Benzoyloxyethyl) norfenfluramine (S-780) was administered to rats by stomach tube at a dose of 50 mg kg−1 of body weight. Livers of the rats which were given an acute dose of the drug synthesized more triacylglycerol, phosphatidylcholine and phosphatidylethanolamine from [1,3-3H]glycerol and [14C]palmitate than did those of control rats. The measurements were made by injecting a mixture of the radioactive precursors into the portal veins of anaesthetized rats and freeze clamping a portion of the liver 1 min later. Different results were obtained after treating rats daily with S-780 for 5 days. Liver slices from these rats synthesized less triacylglycerol and relatively more phosphatidylinositol plus phosphatidyl-serine from [3H]glycerol than did those of control rats. S-780 treatment depressed the hepatic synthesis of phosphatidylcholine and phosphatidylethanolamine as measured in vivo after intraportal injection of [14C]palmitate and [3H]glycerol. Chronic treatment with S-780 also depressed food intake and lowered liver weight and body weight of rats fed the 41B diet. The results are discussed in relation to the effects of S-780 on the synthesis of glycerolipids.
The stability of cannabis and its preparations on storage
Authors: Fairbairn J W , Liebmann J A , Rowan M G 
Published: April 2011

Abstract
Solutions of pure cannabinoids, nine samples of herbal and two of resin cannabis (one freshly prepared) were stored in varying conditions for up to 2 years. Exposure to light (not direct sunlight) was shown to be the greatest single factor in loss of cannabinoids especially in solutions, which should therefore be protected from light during analytical and phytochemical operations. Previous claims that solutions in ethanol were stable have not been substantiated. The effect of temperature, up to 20°, was insignificant but air oxidation did lead to significant losses. These could be reduced if care was taken to minimize damage to the glands which act as “well filled, well closed containers”. Loss of tetrahydrocannabinol after exposure to light does not lead to an increase in cannabinol, but air oxidation in the dark does. It is concluded that carefully prepared herbal or resin cannabis or extracts are reasonably stable for 1 to 2 years if stored in the dark at room temperature.
Some formulation factors affecting the tensile strength, disintegration and dissolution of uncoated oxytetracycline tablets
Authors: Esezobo S , Pilpel N 
Published: April 2011

Abstract
A study has been made of the effects of gelatin binding agent and moisture content on the tensile strength, disintegration and dissolution times of oxytetracycline tablets. These properties all increase with the gelatin content, and maximum tensile strengths occur when the tablets contain between 2·5 and 4·5% w/w of moisture. The properties of the tablets depend on their packing fraction and in general, the disintegration and dissolution times are minimal when the packing fraction is between 0·77 and 0·82.
A connection has been established between the disintegration times of the tablets and the time required for 50 % of the drug content to dissolve.
Changes in the particle size distribution during tableting of sulphathiazole powder
Authors: Carless J E , Shear A 
Published: April 2011

Abstract
Five size fractions of sulphathiazole powder (volume surface mean diameter 155, 133, 86, 50 and 41 μm) were compressed into 12 mm diameter tablets on an instrumented single punch tablet machine. The size analysis of the tablet material after compression showed an attrition of the coarser fraction and an agglomeration of the finer fraction. It is postulated that there is a critical particle size where the effects of crushing and bonding cancel each other. The changes in particle size are discussed in relation to some of the compressive characteristics of the powder.
The persistence of dextran 70 in blood plasma following its infusion, during surgery, for prophylaxis against thromboembolism
Authors: Walkley J W , Tillman J , Bonnar J 
Published: April 2011

Abstract
An infusion of dextran (mean molecular weight 70 000) in normal saline (either 1 litre or 500 ml) was given to patients undergoing hysterectomy. The infusion was started at induction of anaesthesia and continued throughout the operation and for up to 6 h thereafter. The rate of elimination of dextran was independent of the dose given. The time to eliminate half the dose was nearly two days and up to 10% was still present in the circulation after one week. The persistence of dextran in the plasma in these amounts and for this length of time may have considerable implications in the prophylaxis of postoperative deep venous thrombosis.
Release of prostaglandin E-like material from perfused mesenteric blood vessels of rabbits
Authors: Grodzińska L , Panczenko B , Gryglewski R J 
Published: April 2011

Abstract
Infusions of noradrenaline (1–3 μg ml−1 min−1) into the mesenteric vascular preparation of the rabbit caused a 2 to 5 fold rise in perfusion pressure and a release of prostaglandin E-like material (3·23 ± 0·65 (s.e.) ng PGE2 equivalents ml−1). Indomethacin (3 μg ml−1) prevented whereas arachidonic acid (0·2 μg ml−1) augmented, the nor-adrenaline-evoked release of a prostaglandin E-like material. The walls of arterioles or precapillary vessels are the proposed site of prostaglandin generation.
Prostaglandins and leucotaxis
Authors: Walker J R , Smith M J H , Ford-Hutchinson A W 
Published: April 2011

Abstract
Freshly prepared solutions of prostaglandin E1 exhibit chemotactic activity against rabbit polymorphonuclear leucocytes harvested from the peritoneal cavity but are devoid of such activity either against similar cells obtained from the rat or against polymorphonuclear leucocytes obtained from the blood of the rabbit, rat and man. Some implications of these findings with respect to the development of inflammatory responses and the mode of action of non-steroidal acidic anti-inflammatory drugs are discussed.
Aggregation of antiacetylcholine drugs in aqueous solution: monomer concentrations in non-micellar drug systems
Authors: Attwood D 
Published: April 2011

Abstract
The self-association of the antiacetylcholine drugs, propantheline bromide, methantheline bromide and methixene hydrochloride in aqueous solution, has been examined by surface tension, light scattering and conductimetric methods. Surface tension graphs were similar to those of conventional surfactants, showing apparent critical micelle concentrations (cmc) at distinct inflection points. Surface tension measurements in the presence of increasing amounts of electrolyte indicated a decrease in the apparent cmc with increase in electrolyte concentration for propantheline bromide. Light scattering curves for propantheline bromide in electrolyte solution showed no significant discontinuity attributable to a cmc. A mode of self association involving aggregate growth by the stepwise addition of monomers was assumed and equilibrium constants for the initial stages of the association were evaluated. An increase in the magnitude of the stepwise association constants with increase in electrolyte concentration was noted. Integration of the light scattering data according to 1n x = ∫co [(M/M app) — 1] dln c (where M and M app are the monomer and apparent aggregate weights respectively and x is the weight fraction of monomers) showed an asymptotic increase in monomer concentration towards a limiting concentration, as the solution concentration, c, was increased. Limiting monomer concentrations determined by this method were in reasonable agreement with the apparent cmcs from surface tension studies. It was not possible to detect a cmc for methantheline or propantheline bromide from conductivity measurements.
Stability of salicylamide-caffeine complex at different temperatures and its thermodynamic parameters
Authors: Donbrow M , Touitou E , Shalom H Ben 
Published: April 2011

Abstract
The stability constants for formation of complexes of salicylamide with caffeine have been measured between 15 and 45°, by means of the solubility method. There was a linear solubility increase at all temperatures but phase diagrams indicated that at 15 and 25° an additional phase was formed which was found to be an insoluble 1: 1 complex. The enthalpies and entropies of interactions were evaluated. They indicate that the interaction is exothermic and enthalpy controlled.
Dihydroxylated metabolites of cannabinol formed by rat liver in vitro
Authors: Fonseka Kanthi , Widman Marianne 
Published: April 2011

Abstract
Cannabinol (CBN) was metabolized in vitro by a 10 000 g supernatant from rat liver. After removal of unchanged CBN and its monohydroxylated metabolites four dihydroxylated metabolites were isolated. By nuclear magnetic resonance and mass spectrometry the compounds were identified as 1“,7-dihydroxy-CBN, 2”,7-dihydroxy-CBN, 3“,7-dihydroxy-CBN and 4”,7-dihydroxy-CBN. Side chain hydroxylation occurred predominantly at C-4″ and C-3″.
Oxidation of aliphatic hydroxylamines in aqueous solutions
Authors: Beckett A H , Purkaystha A Rashid , Morgan P H 
Published: April 2011

Abstract
The effects of pH, buffer constituents, duration of storage, presence of air, heavy metal ions, extracting solvents and various additives and cofactors on the aerial oxidation of some aliphatic primary and secondary hydroxylamines were investigated. Copper ions were particularly effective catalysts of the oxidation reaction. Conditions to minimize this transformation are described.
Black lipid membranes as a model for intestinal absorption of drugs
Authors: Inui Ken-Ichi , Tabara Katsue , Hori Ryohei , Kaneda Akemi , Muranishi Shozo , Sezaki Hitoshi 
Published: April 2011

Abstract
Black lipid membranes were generated in isotonic buffer (pH 4·5 and pH 6·5) from egg phosphatidylcholine and intestinal lipid, and the permeability to salicylamide, salicylic acid, p-aminobenzoic acid and tryptophan of these membranes was studied. Electrical resistance of intestinal lipid membranes was higher than that of phosphatidylcholine membranes. The presence of cholesterol produced an increase in the electrical resistance of black lipid membranes and a small decrease in the permeability of membranes to drugs. The permeability coefficient of salicylamide, an uncharged drug, was much larger than the coefficients of the charged drugs examined. The values for salicylic acid and p-aminobenzoic acid were much larger than comparable values predicted from their partition coefficients. Intestinal lipid membranes were more permeable to acidic drugs than phosphatidylcholine membranes. It is suggested that phospholipids and other lipid components of the small intestine may play an important role in the membrane permeability to acidic drugs. This method may be of interest in studying the complex processes of drug absorption from intestine.
Hydrolysis of digoxin by acid
Authors: Gault M H , Charles J D , Sugden D L , Kepkay D C 
Published: April 2011

Abstract
Predictable hydrolysis of [3H]digoxin-12α occurred in vitro with incubation in HCl or gastric juice. Hydrolysis varied with pH, time, temperature and agitation. Digoxin, the bis- and mono-digitoxosides of digoxigenin and digoxigenin were separated by silica gel thin-layer chromatography using chloroform-ethyl acetate-glacial acetic acid (25:25:1 v/v) and were quantitated by liquid scintillation spectrometry. Hydrolysis with incubation at 37° and pH 3 for 90 min was minimal, but increased with increasing acidity until &gt;70% was hydrolysed at pH 1·2 after 30 min and &gt;96% after 90 min incubation. At pH 0·9, 87% was hydrolysed after 30 min. In vitro hydrolysis in gastric fluid was slightly less than in HCl at the same pH. A volunteer was given 150 μCi[3H]digoxin-12α by nasogastric tube during a pentagastrin infusion when gastric pH was 0·94. He remained on his left side and samples were aspirated at intervals and immediately neutralized. Ethanol-chloroform 50:50 (v/v) extracts of the gastric fluid aspirated after 90 min and of all the urine specimens collected for 5 days were applied to a DEAE Sephadex LH-20 column. The radioactivity appeared in a single peak as digoxigenin in the 90 min gastric aspirate and in all urine specimens. Extensive intragastric hydrolysis of digoxin may occur under conditions of maximum acid output.
Papaver bracteatum Lindley: thebaine content in relation to plant development
Authors: Fairbairn J W , Helliwell K 
Published: April 2011

Abstract
Four thebaine-rich varieties of P. bracteatum have been grown in the open over two seasons and the thebaine distribution in aerial parts examined to determine the most suitable source material for commercial production. The leaves contained only 0·1 to 0·15%; the capsules 0·5 to 3·0% and the bled latex 28 to 53%. The maximum for the latter occurred about 3–4 weeks after petal opening and during the day, at about 15.00 h. A product ‘bractium’ prepared exactly as opium from P. somniferum contained up to 55% thebaine and calculations from the 1974 results gave theoretical yields up to 58 kg of thebaine per hectare. However this is a very labour intensive method; furthermore bled latex only represents about 46% of the total thebaine of the capsule. In addition the pedicels contain significant amounts of thebaine, so that fruiting tops may be recommended as source material. In the capsule the thebaine content reaches a peak 3 to 4 weeks after petal opening and again two weeks later. At this fully ripe stage there is a theoretical yield of 50 kg per hectare. Two further advantages accrue from collection at this time: the ripe seeds can probably be used for similar purposes as poppy seed; and the pericarps at this stage contain no ‘bound thebaine’ (i.e., thebaine insoluble in MeOH:NH4OH but soluble in acetic acid—in unripe capsules bound thebaine represents 18 to 36% of the total thebaine). There is some evidence that, as this perennial plant increases in age, the capacity for thebaine production seems to continue increasing. Storage of raw material, even in ideal conditions, led to a loss of thebaine of 12 to 20% in one year.
Moisture and gelatin effects on the interparticle attractive forces and the compression behaviour of oxytetracycline formulations
Authors: Esezobo S , Pilpel N 
Published: April 2011

Abstract
The tensile strengths of compacts and/or tablets of the individual components and of granules prepared from an oxytetracycline formulation have been measured using the diametral compression test. Employing the theory of tensile strength, proposed by Cheng, it has been shown that increases in both moisture and gelatin contents of compacts and tablets increase the range of the attractive forces that operate between the granules. By studying the effects of moisture and gelatin on the compressional behaviour of the granules, it has been possible to classify them into different types. Fragmentation of granules occurs at packing fractions between 0·745 and 0·835, depending on their gelatin content.
The identification and quantitation of the major metabolites of ethylamphetamine, produced by rabbit liver microsomal preparations
Authors: Beckett A H , Haya K 
Published: April 2011

Abstract
Amphetamine (I), 1-phenylpropan-2-ol (III), phenylacetone (V), N-hydroxyethylamphetamine (VII), and α-methyl-N-(1′-phenylprop-2′-yl)nitrone (VIII) were obtained as metabolic products from the incubation of ethylamphetamine (II) with fortified male rabbit liver 9000 g supernatant fractions. These metabolites were identified by comparing their t.l.c., g.l.c. and g.l.c.-m.s. behaviour to that of reference compounds. A method for the quantitative analysis of the metabolites in mixtures using g.l.c. techniques is described.
Blood and brain concentrations of imipramine, clomipramine and their monomethylated metabolites after oral and intramuscular administration in rats
Authors: Nagy Adam 
Published: April 2011

Abstract
Imipramine and clomipramine were administered to rats by the oral and intramuscular routes as single and multiple doses. The concentrations of both drugs and their active demethylated metabolites desipramine and desmethylclomipramine were measured in blood plasma, blood cells and brain. The concentrations of the metabolites were higher and the concentrations of the parent substances lower after oral than after parenteral administration, both in blood and in brain. In brain imipramine, desipramine and clomipramine during continuous treatment exceeded their plasma concentrations by six to ten times. The corresponding figure for desmethylclomipramine was 1·7. The extent of accumulation of the investigated substances in the brain was independent of the route of administration.
Effect of lofepramine and other antidepressants on the uptake of 5-hydroxytryptamine and noradrenaline into rat brain monoaminergic neurons
Authors: Segawa Tomio , Nomura Yasuyuki , Tanaka Akiyoshi , Murakami Hiroko 
Published: April 2011

Abstract
Lofepramine, (N-methyl-N-[4-chlorobenzoylmethyl]-3-[10, 11-dihydro-5H-dibenz(b,f)-azepin-5-yl]-propylamine hydrochloride), is a new antidepressant with low toxicity and no peripheral anticholinergic activity. Its effect on 5-hydroxytryptamine (5-HT) and noradrenaline uptake into rat brain monoaminergic neurons was studied and compared with that of other antidepressants, particularly with that of imipramine and desipramine. Lofepramine inhibited both 5-HT and noradrenaline uptake into synaptosomal fractions in vitro but was 4 times more potent in inhibiting noradrenaline than 5-HT uptake, indicating the effect resembles that of desipramine. Noradrenaline uptake was also preferentially inhibited in synaptosomes from brain of rats treated previously with lofepramine or desipramine (i.p.). Pretreatment with SKF 525A (i.p.) did not diminish the effect of lofepramine but rather potentiated it. Therefore it is suggested that the formation of desipramine is not necessary for lofepramine to exhibit the effect on amine uptake in vivo. Both lofepramine and desipramine inhibited intraventricular noradrenaline uptake into synaptosomes without any effect on 5-HT uptake. These results suggest that lofepramine is qualitatively similar to desipramine with respect to preferential inhibition of noradrenaline uptake into central noradrenergic neurons.