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PubMed2002

HPLC assay of acetylsalicylic acid, paracetamol, caffeine and phenobarbital in tablets.

This paper present a HPLC method for simultaneous determination of acetylsalicylic acid, paracetamol, caffeine and phenobarbital in tablets, using chromatographic system consisting a Bio Rad 18 01 solvent pump, Rheodine 71 25 injector and Bio Rad 18 01 UV-Vis Detector. Separation was achieved using Bio SiL HL C18, 5 microm, 250 x 4.6 mm column. Mixture of acetonitrile-water (25:75 v/v) adjusted to pH 2.5 with phosphoric acid was used as a mobile phase at a flow rate of 2.0 ml min(-1). UV detection was at 207 nm range 0.01 AUFS. Under the same conditions it was possible to determine the level of salicylic acid. The chromatographic parameters such as retention times, capacity factor, peak asymmetry, selectivity factor and resolution factor was determined. The validation parameters: linearity (r > 0.998), intra-day precision (RSD: 0.36-1.89%) and inter-day precision (RSD: 0.58-2.18%), sensitivity (LOD: 9 x 10(-5)-1.7 x 10(-4) mg ml(-1) and LOQ: 2.5 x 10(-4)-5.6 x 10(-4) mg ml(-1)), accuracy (recoveries: 98.35-99.14%) and reproducibility (recovery values: 98.74-102.08% for acetylsalicylic acid, 99.93-102.11% for paracetamol, 98.25-102.12% for caffeine and 98.15-102.3% for phenobarbital) (RSD: 1.21-1.85%) were found to be satisfactory. The proposed HPLC method has been applied for the determination of acetylsalicylic acid, paracetamol, caffeine and phenobarbital in Malophenum tablets. The obtained RSD values were within 0.99-1.21%. The developed method is rapid and sensitive and therefore suitable for routine control of these drugs in dosage form.

Acetaminophen↗
PubMed1989

The effect of hydroxyethylrutoside and its combination with acetylsalicylic acid in patients with obliterative atherosclerosis.

The effect of 7-mono-hydroxyethylrutoside and its combination with acetylsalicylic acid was evaluated in a controlled clinical trial, performed in 105 patients with obliterative atherosclerosis of the lower limbs, and using non-invasive measurement of peripheral haemodynamic parameters--blood flow during reactive hyperaemia and ankle systolic blood pressure. Patients, randomized into three groups, received either placebo or 7-mono-hydroxyethylrutoside alone or in combination with acetylsalicylic acid for 12 months. The placebo group showed a decrease in maximum calf blood flow and a decrease in ankle systolic pressure. Administration of 7-mono-hydroxyethylrutoside did not lead to any significant changes in systolic pressure but there was a decrease in the maximum calf blood flow. There were no statistically significant changes in patients receiving the 7-mono-hydroxyethylrutoside and acetylsalicylic acid combination who, by contrast, showed a tendency to increased values of the parameters measured.

Adult↗
PubMed1984

Low-dose acetylsalicylic acid (100 mg/day) after aortocoronary bypass surgery: a placebo-controlled trial.

The effect of low-dose acetylsalicylic acid (100 mg/day) upon bypass patency-rate and clinical course after aortocoronary bypass surgery was investigated in a randomized, placebo-controlled clinical trial. Sixty patients with 143 distal anastomoses of bypasses were randomized, 46 underwent repeat angiography after 4 months. Using the intention to treat-strategy, treatment was superior to placebo as judged by bypass patency rate and occurrence of cardiovascular complications or death. Counting the six drop-outs as failures, only nine of the 31 patients of the placebo group, but 16 of the 29 patients of the treatment group were considered successes (P less than 0.04). Eighteen patients in the placebo group and eight patients of the treatment group received beta-adrenoceptor blockers postoperatively, suggesting again a favourable effect of the treatment. Adverse drug reactions were very rare and minor. Supported by pathophysiological insights and positive trends in similar trials, the positive result justifies the recommendation of prescribing 100 mg of acetylsalicylic acid once daily to all patients without contraindications after aortocoronary bypass surgery. The positive result of this trial warrants further clinical trials of low-dose acetylsalicylic acid for other indications in arterial diseases.

Aspirin↗
PubMed1994

A ceramic system for continuous release of acetylsalicylic acid.

This investigation was conducted to study the release of acetylsalicylic acid (ASA) from a beta-Tricalcium Phosphate (TCP) resorbable ceramic matrix (RCM) in Tris-HCl (pH 7.4, 0.5M) at 37 degrees C. Initial compression load studies were conducted for 12 hours. Compression load and dose-response studies were conducted for a total duration of seven days. Mixtures of 150 mg acetylsalicylic acid (Aspirin) and 500 mg TCP were compressed at loads of 2000, 3000, or 4000 lbs. Ceramics with 75, 150, 225, 300, or 375 mg of ASA were mixed with 500 mg TCP and compressed at 3000 lbs. Aliquots of Tris-HCl, taken at two hour intervals for the first 12 hours, and daily thereafter, were assayed spectrophotometrically for ASA at 245 nm. Differences in the amounts of ASA released by RCMs compressed at the three loads were not significant. Release of ASA from RCMs was linear only if the ceramic/ASA ratio was close to 6.67:1. Results of this investigation suggest that resorbable TCP ceramics can be used for continuous delivery of ASA for seven days.

Aspirin↗
PubMedDate not supplied

Sequential determination of salicylic and acetylsalicylic acids by amperometric multisite detection flow injection analysis.

An amperometric multisite detection flow injection analysis (FIA) system was developed for sequential determination of 2 analytes with a single sample injection and single detector. Tubular composite carbon electrodes with an inner diameter similar to that of the FIA manifold tubing were constructed so that measurements could be made without impairing the sample plug hydrodynamic characteristics. The electrochemical behavior of the tubular voltammetric cell in a low-dispersion FIA manifold and the behavior of the FIA system incorporating this type of voltammetric cell intended for multisite detection were evaluated by performing measurements with potassium hexacyanoferrate(II). Feasibility of the approach was demonstrated in the sequential determination of salicylic and acetylsalicylic acids in pharmaceutical products at a fixed potential of 0.98 V. The system allows sequential determination of salicylic acid concentrations ranging from 1.0 x 10(-5) to 5.0 x 10(-5) M and acetylsalicylic acid concentrations between 1.0 x 10(-3) and 5.0 x 10(-3) M with good precision on both detection sites and with relative standard deviations (RSDs) > or = 1.5% (n = 10) and 2.1% (n = 10), respectively. A comparison of these results with those of the U.S. Pharmacopeia procedure showed RSDs <5.0 and 1.0% for salicylic acid and acetylsalicylic acid, respectively. The proposed method enables 15 determinations per hour, which corresponds to the analysis of approximately 8 samples per hour. The detection limits of the methodology were approximately 3.5 x 10(-6) and 1.1 x 10(-5) M, respectively, for the first and second monitoring sites.

Aspirin↗
PubMed1980

"In vivo" effects of acetylsalicylic acid and two ether derived compounds on primary immune response and lymphoblastic transformation.

A comparison was performed of acetylsalicylic acid and two ether derivatives (Benorilate and Eterilate) and indomethacin in order to ascertain the in vivo effects on the lymphoblastic transformation and the primary immune response in mice. The humoral response in Benorilate-and Eterilate-treated mice was 40-50% lower than that of the controls, whereas in acetylsalicylic acid-treated mice the response was only 25% inhibited. The number of immunoglobulin synthesizing cells was neither reduced by acetylsalicylic acid nor by its derivatives, although indomethacin treatments (used for comparative purposes) inhibited by 40% the number of direct plaque-forming cells on the days tested. Mitogen-induced proliferation of spleen lymphocytes was also inhibited in the treated mice; these inhibitions were negligible in the case of cells from acetylsalicylic acid-treated mice activated by concanavalin A and slight in cells from Benorilate-treated mice activated by bacterial lipopolysaccharide. When lymphocytes from drug-treated animals were further cultured in the presence of the same drug, a variable inhibition of mitogen-induced proliferation was observed. These different in vivo effects of acetylsalicylic acid and the two ether derivatives and indomethacin may be due to a distinct action on diverse lymphocyte subpopulations altering their cellular collaborative interactions or modifying the prostaglandin availability.

Acetanilides↗
PubMed1985

Clinical-pharmacokinetic investigations of acetylsalicylic acid in cases of imminent premature delivery.

The pharmacokinetics of acetylsalicylic acid have been examined in a dose of 3.6 g per day (0.9 g every 6 h) for 4 days, and the effect of the drug in 25 gravidae, threatened by premature delivery, has also been studied. Salicylate in maternal blood was higher than in amniotic fluid, umbilical cord and foetus at birth. It is concluded that 9 h after a dose of 3.6 g acetylsalicylic acid, the salicylate level in maternal blood was sufficient to reduce the number of uterine spasms in most patients. No effect of the drug on blood coagulation in mother or child was observed.

Amniotic Fluid↗
PubMed1983

[Gastric microhemorrhage and acetylsalicylic acid. Prevention using prostaglandin E2].

The possible prophylactic effect of prostaglandin E2 (PGE2) pretreatment against gastric microbleedings caused by acetylsalicylic acid was investigated in six healthy volunteers. Gastric microbleeding rate was determined by the gastric tube technique of Fisher and Hunt, at first without any medication. The test was repeated after a two-day intake of acetylsalicylic acid (four times 0.5 g/d) and after two days of the same dose, 15 minutes after the administration of PGE2 (four times 0.5 mg/d). Between the two treatment periods, their sequence randomized, there was a treatment-free pause of at least eight days. Basic gastric microbleeding rate was 0.42 +/- 0.10 ml/d (means +/- Smeans). After administration of acetylsalicylic acid this rose highly significantly elevenfold (4.59 +/- 1.64 ml/d). Prophylactic administration of PGE2 prevented this rise (0.24; 0.04-2.55 ml/d) (median; 10th-90th percentile). There were no side effects to the administration of PGE2.

Adolescent↗
PubMed1981

[Control of implantation in rats and sows by peroral administration of prostaglandin synthetase inhibitors. 2. Effects of prostaglandin F2 alpha, progesterone/estrone, and acetylsalicylic acid on implantation and various biochemical parameters of amniotic fluid in the rat].

The highest pregnancy rate as well as most of all implantates and lowest foetal loss were recorded from the prostaglandin F2 alpha-(PGF2 alpha)-group (84, 84, and 16 per cent), while values following progesterone/oestrone and acetylsalicylic acid treatment were below those obtained from the controls. The highest number of normally developed (97 per cent) and the lowest number of degenerated foetuses (three per cent) were recorded following acetylsalicylic acid treatment, as compared to the control group (91 and nine per cent). Application of prostaglandin had no adverse effect on foetal development. The overall protein concentration in the amniotic fluid, following injection of progesterone/oestrone and PGF2 alpha, was lower with significance than the control value. Acetylsalicylic acid caused slight but insignificant rise in protein concentrations. The behavior of glucose concentrations in the amniotic fluid seemed to be diametrically opposed to that of protein. The activity of acid phosphatase was low and highly variable in all four experimental groups. Values moderately increased over the controls were recorded from the acetylsalicylic acid group.

Acid Phosphatase↗
PubMed1995

[Adverse effects of combined use of acenocoumarol and acetylsalicylic acid after myocardial infarct and unstable angina].

The authors examined the bleeding complications in 75 patients who received acenocoumarol and acetylsalicylic acid combined therapy. The studied population suffered from either acute myocardial infarction or unstable angina. Among the 75 patients in two cases (2.7%) appeared serious bleeding and in another 25 cases (33.3%) mild bleeding complications. There were no fatal cases. Comparing these data with literary data, the authors stated that in the study group the proportion of serious complications didn't increase in comparison with patients who received either acenocoumarol, warfarin or acetylsalicylic acid but mild bleeding appeared more frequently. This finding suggests that in high risk patients the combined acenocoumarol-acetylsalicylic acid therapy can be considered under strict control.

Acenocoumarol↗
PubMed2000

Acetylsalicylic acid effervescent 1000 mg (Aspirin) in acute migraine attacks; a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group study.

In this multicentre, randomized, double-blind, single-dose study a total of 374 patients generally suffering from migraine attacks suitable for treatment with non-prescription drugs, received either oral acetylsalicylic acid effervescent 1000 mg (ASAE) or effervescent placebo for the treatment of an acute migraine attack. Of the 343 patients fulfilling the criteria for efficacy analysis 169 patients took acetylsalicylic acid and 174 placebo. Response rates (reduction of headache severity from severe or moderate to mild or no pain at 2 h after administration) were 55.0% for acetylsalicylic acid and 36.8% for placebo (P < 0.001). Twenty-nine percent of patients in the active treatment group were pain-free after 2 h compared with 16.7% in the placebo group (P = 0.007). No headache recurred within 24 h post-dose in 84.6% of patients in the active group and in 85.1% of patients in the placebo group. Effervescent placebo reduced nausea and vomiting to the same degree as the active drug. Adverse events of acetylsalicylic acid (8.3%) were generally mild or moderate and comparable to those of placebo (2.9%). This study shows that oral ASAE is safe and effective for the treatment of acute migraine attacks.

Acute Disease↗
PubMed1979

[Acetlysalicylic acid, protective antacid effect and lesions of the gastric mucosa. Effect of acetylsalicylic acid and an antacid drug (Gastropulgit Tabs) on the transmural electric potential in the human stomach].

Antacids are able to prevent acetylsalicylic acid-induced functional and morphological changes of the gastric mucosa. In order to test whether a new antacid in chewing-tablet form (Gastropulgit Tabs) might be able to protect the gastric mucosa from acetylsalicylic acid-induced functional changes similarly to liquid antacids the effect of this antacid on acetylsalicylic acid-induced changes of transmural gastric potential difference was measured in healthy volunteers. The decrease of transmural potential differences induced by 640 mg acetylsalicylic acid could be prevented by simultaneous addition of 2 tablets of Gastropulgit Tabs. Thus the antacid in tablet form is able-like liquid antacids-to protect the gastric mucosa against acetylsalicylic acid-induced functional changes.

Alum Compounds↗
PubMed1996

Intestinal permeability changes in response to acetylsalicylic acid in relatives of patients with Crohn's disease.

BACKGROUND & AIMS: Presence of a familial intestinal permeability defect in Crohn's disease remains controversial despite numerous studies. The purpose of this study was to determine whether detection of a permeability defect in first-degree relatives of patients with Crohn's disease can be enhanced using an acetylsalicylic acid provocation test. METHODS: Lactulose-mannitol ratio, a measure of intestinal permeability, and total sucrose excretion, a measure of gastroduodenal permeability, were determined before and after ingestion of acetylsalicylic acid in healthy controls, in patients with Crohn's disease, and in the first-degree relatives of patients with Crohn's disease. Subjects were classified as hyperresponders if their results were above the mean of + 2SD of the controls. RESULTS: First-degree relatives had a 110% increase in intestinal permeability after acetylsalicylic acid compared with an increase of 57% in controls (P = 0.001). Thirty-five percent of relatives were classified as hyperresponders. There was no significant difference in the change in sucrose excretion between relatives and controls (259% vs 198%; P < 0.05). CONCLUSIONS: First-degree relatives of patients with Crohn's disease have an exaggerated increase in intestinal but not gastroduodenal permeability in response to acetylsalicylic acid. This study supports a familial permeability defect in Crohn's disease, which may not be present in all families.

Adult↗
PubMed1987

Tolerance to acetylsalicylic acid (ASA) induced in ASA-sensitive asthmatics does not depend on initial adverse reaction.

A state of tolerance to aspirin (ASA) was induced in 10 aspirin-sensitive patients by daily administration of incremental doses of ASA. No adverse reactions were reported. The initial dose (from 5 to 60 mg) was gradually increased each day up to 300 mg and then doubled. 50 mg indomethacin given the day after administration of 600 mg ASA did not elicit any symptom of intolerance. The authors discuss a possible mechanism of tolerance to aspirin in ASA-sensitive asthmatics after ASA administration, suggesting that it might be connected either with inhibition of the lipooxygenetic pathway of arachidonic acid metabolism or with blockade of the cyclooxygenase supplementary binding site by salicylic acid, a product of acetylsalicylic acid hydrolysis. This would prevent aspirin from binding with the catalytic cyclooxygenase site.

Adult↗
PubMed2003

The effects of ursodeoxycholic acid alone and ursodeoxycholic acid plus low-dose acetylsalicylic acid on radiolucent gallstones.

BACKGROUND/AIMS: Mucin, a high molecular weight glycoprotein secreted by the gallbladder and biliary duct epithelium, is a pronucleating agent in experimental and human gallstone disease. Blockage of mucin release with aspirin inhibits the formation of primary gallstones in animal models. The aim of this study was to compare the effects of ursodeoxycholic acid alone and plus low-dose aspirin on dissolution of solitary or multiple gallstones. METHODS: There were three treatment groups comprising 43 patients with cholesterol gallstones: Group I (n=16, 13 females, three males) was given ursodeoxycholic acid (15 mg. kg. day) alone and Group II (n=14, 12 females, two males) was treated with aspirin (100 mg/day) in addition to ursodeoxycholic acid cholic. Group III was a control group of 13 cases (11 females, two males) who were monitored without medical treatment. Stone dissolution rates were evaluated sonographically in all patients at three month intervals during the treatment period. RESULTS: After 12 months of treatment, stone dissolution was found in six (37.5%) of the patients in Group I and six (42.8%) of the patients in Group II. The difference in both treatment groups was significant compared to controls (p<0.05) but there was no significant difference between the two treatment groups (p>0.05). Of the cases in whom dissolution was achieved, all patients had multiple gallstones except for one with a solitary stone in Group I. Gallstones were not dissolved of any subject of group III. CONCLUSIONS: The results showed that ursodeoxycholic acid cholic therapy is more effective in the dissolution of multiple gallstones than of solitary ones. Combination with aspirin did not potentiate the efficacy of ursodeoxycholic acid cholic.

Adult↗
PubMed1983

Endoscopic evaluation of the comparative effects of acetylsalicylic acid and choline magnesium trisalicylate on human gastric and duodenal mucosa.

A new salicylate product, choline magnesium trisalicylate (Trilisate tablets), and acetylsalicylic acid were compared for their local effects in equipotent doses on the gastroduodenal mucosa in a randomized, double-blind, cross-over study, using 10 healthy volunteers. After five-day periods of administration, gastroduodenoscopy was performed and photographs were obtained. All subjects given acetylsalicylic acid developed multiple mucosal lesions, but in only four subjects given choline magnesium trisalicylate were slight mucosal changes noted. Mean serum salicylate levels were similar in the two groups. Our data suggest that the risk of developing mucosal lesions is much less during treatment with choline magnesium trisalicylate than with acetylsalicylic acid.

Adult↗
PubMed1990

Dipyridamole alone or combined with low-dose acetylsalicylic acid inhibits platelet aggregation in human whole blood ex vivo.

1. In a randomized, double-blind trial we compared the inhibition of the platelet-vessel wall interactions in whole blood ex vivo. There were four groups of 24 healthy volunteers each of whom were treated orally for 3.5 days with either 200 mg dipyridamole (sustained release preparation), 25 mg acetylsalicylic acid, both drugs combined or placebo twice daily. 2. The mean area of all platelets/aggregates was reduced by 6.2% +/- 4.2% (+/- s.e. mean) by placebo (n = 23), 19.8% +/- 6.7% by dipyridamole (n = 22), 53.7% +/- 4.9% by acetylsalicylic acid (n = 23) and 71.4% +/- 3.7% by the combination of both drugs (n = 24), when compared with total inhibition of aggregation by EGTA. Thus, low-dose acetylsalicylic acid inhibited aggregation (P less than 0.001). 3. Dipyridamole reduced the size of platelet aggregates (P less than 0.01, two-fold analysis of variance). The reduction was correlated with the individual dipyridamole plasma levels (P less than 0.05, analysis of covariance). The subgroup of large and very large thrombi being formed was also reduced by dipyridamole (P less than 0.05). 4. This ex vivo study demonstrates that dipyridamole alone inhibits formation of thrombi on subendothelial matrix and enhances the inhibitory effect of low dose acetylsalicylic acid in this model of thrombosis.

Adult↗
PubMed1982

Effects of sodium salicylate and acetylsalicylic acid on intramural pH and ulceration of rabbit antral mucosa.

This study examines the relationship between the pH within the middle third of antral mucosa (intramural pH [IMpH]) and the development of ulceration caused by salicylates. Luminal soldium salicylate does not significantly alter the IMpH or cause ulceration of mucosa maintained at luminal pH 7. Salicylate at pH 3.5 initially decrease IMpH (7.28 to 6.75), during which time ulceration occurs. IMpH subsequently increase, resulting in profound alkalinization (pH 7.67) associated with increased HCO3 secretion. Salicylate at pH 1 causes a sustained decrease in IMpH (6.57), which is associated with more severe ulceration. Neither sodium salicylate nor acetylsalicylic acid given intravenously affects. IMpH or causes ulceration at luminal pH 7 or 3.5. However, at pH 1 both salicylate compounds cause ulceration and subtle changes in net ion fluxes without altering IMpH. The data suggest that acidification of the midportion of the mucosa in general is not a prerequisite for the occurrence of gross damage, and the damaging effects of intravenous salicylates cannot be explained by thier metabolic actions alone. However, it appears that the metabolic effects of salicylate make the mucosa more susceptible to the deleterious effects of diffusing acid. Since intravenous sodium salicylate and acetylsalicylic acid both cause ulceration but only acetylsalicylic acid alters prostaglandin synthesis, interference with prostaglandin metabolism does not appear to be a prerequisite for the occurrence of ulceration.

Animals↗