Aspirin Enteric-coated Tablets Research Articles

Gastric injury caused by low-dose aspirin therapy in consecutive Japanese patients: a prospective study

Low-dose aspirin (<325 mg/day), administered to those with several conditions involving ischemic disorders, can cause upper gastrointestinal (GI) complications. In this prospective study, we aimed to clarify the incidence of aspirin-induced gastric ulcers in consecutive Japanese patients and identify suitable preventive measures. We recruited 125 consecutive adult outpatients who received low-dose aspirin (enteric-coated tablets 100 mg) for >8 weeks. Endoscopy and blood tests were used to evaluate their gastric injury (which was scored using a modified Lanza scale) and anti-Helicobacter pylori antibody titer, respectively. We found that 39.8% of patients received either no upper GI drug or only mucoprotective drugs, 39.8% received medium-dose histamine H2 blockers, and 20.4% received proton-pump inhibitors (PPIs). Anti-H. pylori antibody titers were positive in 43.7% of patients. The incidence of definitive gastric ulcers in this population was 0.97%. Ordered logistic regression analysis revealed that the odds ratio for the increase in the modified Lanza score was 0.20 for medium-dose histamine H2 blockers and 0.09 for PPIs. The incidence of postoperative definitive gastric ulcers in Japanese patients receiving ≤100 mg enteric-coated aspirin was 0.97%. The use of PPIs and histamine H(2) blockers may prevent aspirin-induced gastric injury in such patients.

SIMULTANEOUS DETERMINATION OF ASPIRIN AND ITS METABOLITE FROM HUMAN PLASMA BY UPLC-UV DETECTION: APPLICATION TO PHARMACOKINETIC STUDY

A rapid and sensitive liquid chromatography method with UV detection for simultaneous measurement of aspirin (ASA) and salicylic acid (SA) was developed and validated completely in human plasma. ASA, SA, and Benzoic acid (BA) as internal standard were extracted via protein precipitation with Perchloric acid. An isocratic elution with binary mode was used to separate interference peaks using a C18 Acquity column with only three minutes of analysis time. The linearity range was 15 to 6000 n g mL−1. Calibration functions, LOQ, stability, intra- and inter-day reproducibility, and accuracy were estimated. The inter- and intra-day % CV for ASA and SA are ±15% and the percentage change of all stability samples with comparison samples were within 10%. The in vitro conversion of ASA to SA was also studied and it was controlled to keep at a minimum (<10%). With respect to other published methods this method is most sensitive in UV detection, as well as its sensitivity and throughput is comparable or even better than published LC-MS/MS methods. This method was successfully applied to a single dose Bioequivalence (BE) study of following administration of 81 mg enteric coated Aspirin tablets.

Acetyl salicyclic acid (aspirin) improves synthesis of maspin and lowers incidence of metastasis in breast cancer patients

Maspin, a 42 kDa protein produced in normal breast cells, has been shown to inhibit the invasion and metastasis of breast cancer in an animal model. Ingestion of acetylsalicylic acid (aspirin) by breast cancer patients has been reported to restore the systemic synthesis of maspin through the stimulation of systemic nitric oxide production. Studies were carried out to determine the effect of aspirin on the incidence of breast cancer metastasis, which is reported to occur in 50% of patients who have previously received chemotherapy, radiation, and/or surgery. Thirty-five female patients (aged 41-65 years) with breast cancer who had previously received these therapies took one 75 mg/70 kg body weight enteric-coated aspirin tablet every 24 h, after an adequate meal, for 3 years. Their plasma nitric oxide and maspin levels were measured. The occurrence of metastasis was ascertained monthly by a qualified oncologist, and confirmed, if necessary, by biopsy. Daily ingestion of aspirin by participants resulted in an increase in maspin levels from 0.95 ± 0.04 to 4.63 ± 0.05 nM after 24 h. These levels were maintained for 3 years. These studies suggest that daily ingestion of aspirin might significantly reduce the incidence of breast cancer metastasis in patients who have previously received anticancer therapies.

Feasibility of conducting a primary prevention trial of low‐dose aspirin for major adverse cardiovascular events in older people in Australia: results from the ASPirin in Reducing Events in the Elderly (ASPREE) pilot study

To determine the feasibility of performing a large clinical trial of the use of aspirin for the primary prevention of cardiovascular disease in older participants--the ASPirin in Reducing Events in the Elderly (ASPREE) trial. A randomised double-blind placebo-controlled pilot trial of 100 mg of enteric-coated aspirin tablets daily, in men and women aged 70 years and over who did not have overt cardiovascular disease, and who were followed for 12 months. Participants were identified from the computer databases of general practitioners who were co-investigators in a previous trial. The Melbourne metropolitan area between March 2003 and June 2005. The level of response to participation by GPs; the level of response from potential trial participants; the screening-to-randomisation rate to ensure the recruitment target could be achieved; and the retention of participants in the trial after 12 months. Forty-two GPs (23% of 180 mailed) expressed interest in participating in the pilot trial. Nineteen became co-investigators, of whom six were not required to meet recruitment targets. Letters were sent to 2614 patients, of whom 243 were screened and 209 (86%) were randomly allocated to receive aspirin or placebo. At 12 months,192 (92%) returned for follow-up, and 153 of these (80%) were still taking trial medication. There was a significant reduction in mean haemoglobin level in those taking aspirin. The recruitment strategy for ASPREE, based on methods developed for the conduct of a previous large-scale trial conducted in general practice, was successfully redeployed in this pilot study, with improved efficiency resulting from computerised database searching, telephone pre-screening, a simpler run-in phase and participant familiarity with the trial drug. We conclude that conducting ASPREE in Australian general practice with 18 000 participants is feasible. International Standard Randomised Controlled Trial Number Register ISRCTN83772183.

Comparison of four laboratory methods to assess aspirin sensitivity

The purpose of this study was to compare the ability of four commercial platelet function assays to detect aspirin response in normal individuals taking 81 or 325 mg aspirin in a single-dose response and then in a 7-day dosing regimen. We employed the Chronolog 570VS whole-blood aggregometer with agonists 1.0 microgram/ml collagen and 0.5 mmol/l arachidonic acid, the PFA-100 epinephrine/collagen cartridge closure time, the Accumetrics Verify/Now arachidonic acid cartridge, and the urine 11-dehydrothromboxane immunoassay normalized to urine creatinine. Fifty normal individuals who met the inclusion criteria were consented in the single-dose study. Blood and urine were collected at baseline, and then each participant was given a 81 mg enteric-coated aspirin tablet. Blood and urine were collected after 24 h. After a minimum of 14 days the process was repeated with a 325 mg aspirin dose. Forty-five individuals were enrolled in the 7-day study. Blood and urine were collected at baseline. Then each participant was given an 81 mg dose of aspirin daily for 7 days. After 7 days, blood and urine specimens were obtained and tested. After a minimum washout period of 14 days the process was repeated using a 7-day regimen of 325 mg enteric-coated aspirin tablet. Student's t-test indicated statistical significance between baseline and post responses in both dosing regimens (P < 0.05). Individuals were not consistently identified as aspirin responsive across all platforms. All assays discriminated between platelet response and nonresponse to aspirin at both dosages. It may be necessary to employ multiple assays to detect individual platelet response.

Efficacy and safety of aspirin in prevention of venous thromboembolism after total joint arthroplasty

To study the efficacy and safety of aspirin in prophylaxis of venous thromboembolism (VTE) after total joint arthroplasty. 240 patients who received total joint arthroplasty, 157 undergoing total knee arthroplasty (TKA) and 83 undergoing total hip arthroplasty (THR), were divided into 2 basically matched groups, Group A (n = 100), receiving aspirin enteric-coated tablets 100 mg/day since the first day after operation till discharge 10-14 days after operation, and Group B (n = 140), receiving subcutaneous injection of low molecular weight heparin (LMWH) once daily for 10 d. The effects and safety were evaluated. 13 patients (13.0%) were diagnosed with deep venous thrombosis (DVT) in Group A, 7 of them were symptomatic, 3 were suspected of pulmonary embolism, and 2 suffered from cardio-cerebrovascular event. In Group B, 10 patients (7.1%) had DVT, 4 of them were symptomatic; suspicious pulmonary embolism and cardio-cerebrovascular event were diagnosed in 3 and 8 patients respectively. There were no statistic significances between the two groups in all these aspects. The quantity of bleeding, decrease of hemoglobin, hematoma rate, and infection rate of Group A were (693.4 +/- 480.1) ml, (32.9 +/- 18.0) g/L, 1%, and 0% respectively, all not significantly different from those of Group B (648.9 +/- 521.1) ml, (36.4 +/- 21.9) g/L, 2.1%, and 1.4% respectively, all P > 0.05. Aspirin is as effective as LMWH in venous thromboembolism prophylaxis after total joint arthroplasty. In addition, aspirin is cheap, administered orally, well tolerated, without necessity for surveillance, and with good compliance and potential of prevention of cardio-cerebrovascular events.

Pyloric stenosis: hold-up of enteric coated aspirin tablets.

Abstract The case is presented of a 68-year-old woman with adult hypertrophic pyloric stenosis who ingested 66 enteric coated 650-mg. aspirin tablets over the course of 11 days immediately prior to her admission to hospital. Most of these tablets remained intact in the hugely dilated obstructed stomach and were recovered at emergency gastrotomy. The mechanism of disintegration of enteric coated tablets and the possible consequences of en masse disintegration of these ingested tablets are discussed.

Clinical study on influence of Buyang Huanwu Decoction on the metabolic imbalance of endothelin and calcitonin gene related peptide in patients with early cerebral infarctionon the metabolic imbalance of endothelin and calcitonin gene related peptide in patients with early cerebral infarction

Objective: To explore the mechanism of Buyang Huanwu Decoction (BHD) in treating early cerebral infarction.Methods: Seventy cases with early cerebral infarction were randomly divided into two groups. Chinese medicine group (CMG, n = 35) was treated with BHD; western medicine group (WMG, n = 35) was treated with hydroxyethyl starch injection and enteric coated aspirin tablets. The levels of endothelin (ET) and calcitonin gene related peptide (CGRP) in plasma before and after treatment and the results of clinical treatment were observed. Also healthy subjects were used as the normal control.Results: The levels of ET before treatment in the two treated groups were significantly higher than that of the healthy subjects (P<0. 001), and the levels of CGRP were significantly lower (P < 0.001). After treatment the metabolic imbalance of ET and CGRP improved significantly in the two treated groups (P<0. 001), but the ET and CGRP in CMG improved more obviously than those in WMG (P<0.01, P<0.05). The markedly effective and curative rate of CMG was higher than that of WMG (68. 6 % vs 31.4 %; ϰ2 = 9. 65, P < 0. 01).Conclusion: BHD could improve the metabolic imbalance of ET and CGRP in patients with early cerebral infarction and on the virtue of this mechanism it could be used to treat cerebral infarction.

A comparative bioavailability study of different aspirin formulations using on-line multidimensional chromatography

A multi-dimensional column chromatographic method employing UV spectrometric detection was optimised and successfully used in a comparative bio-availability study of aspirin obtained from different commercially available oral dosage forms. Sample clean-up was achieved by on-line solid-phase extraction. In this study, the bioavailability of aspirin was compared in plain aspirin tablets, chewed tablets, effervescent tablets and Enteric-coated aspirin tablets. Blood samples were taken at frequent intervals after single dosing in ten healthy volunteers, the plasma samples were first treated with physostigmine sulphate to minimise enzymatic hydrolysis of aspirin to salicylate. The results showed the measured T max, C max and AUC was significantly higher for soluble aspirin than for the other formulations and the t 1/2 was shorter. This indicates the rapid absorption of aspirin from a soluble formulation compared with that from the other formulations. These differences suggest that the soluble formulation could be the aspirin of choice to treat patients suspected to be at high risk of myocardial infarction. The method performs, in a single step, an efficient extraction and clean-up of aspirin from human plasma. The calibration graph was linear over the calibration range 0.2–12 μg ml −1 plasma with a limit of detection of 0.1 μg ml −1. The intra- and inter-assay coefficients of variation were less than 6% and the recoveries ranged from 86 to 98%. The proposed method combines the advantages of being simple and selective in the presence of other potential interfering drugs and is suitable for routine analyses to obtain valuable information about the clinical effects of the drug and its use in prevention treatments of acute myocardial infarction. The whole procedure takes ∼7 min and is in agreement with other conventional methods.

Antiulcer Therapy

Perhaps older drugs to treat ulcers, such as antacids, are just as effective as the newer drugs, but veterinarians have all but abandoned these drugs in favor of H2-receptor antagonists, sucralfate, and omeprazole. For most patients, one of the H2-receptor antagonists or sucralfate is probably the initial drug of choice. For patients refractory to these drugs or for which once-a-day dosing is desirable, omeprazole has an advantage. The doses for these drugs are listed in Table 1. Patients presented with acute bleeding ulcers should be managed with emergency therapy. Fluid therapy and blood transfusions are the essential elements of the initial therapy. Surgical resection of the ulcers may be necessary, and most patients should be administered H2-receptor antagonists or sucralfate while they recuperate. Longer term therapy with antiulcer drugs will depend on the predisposing factors that initiated the ulcers. The practice of lavage of the stomach with iced saline or epinephrine to stop bleeding from gastric ulcers is not effective. A common cause of ulcers in small animals is the administration of NSAIDs. Ulcers caused by these agents should be managed like any other ulcers. Fortunately, if ulcers are diagnosed early, they usually heal once the NSAID is discontinued. Unfortunately, many NSAID-induced ulcers identified postmortem did not produce clinical signs, and the ulcers may not be apparent until severe bleeding occurs. In cases in which patients are at risk for developing ulcers from NSAIDs, there may be an advantage in administering the synthetic prostaglandin misoprostol. In many patients that are sensitive to the GI irritation of NSAIDs, switching from one NSAID to another may alleviate some of the signs. Buffered aspirin may be somewhat less irritating than plain uncoated aspirin but will not completely prevent ulcers. The administration of enteric-coated aspirin tablets to dogs is discouraged, because systemic absorption from these tablets is unpredictable.

Adult respiratory distress syndrome induced by salicylate toxicity.

Noncardiogenic pulmonary edema induced by salicylate toxicity is becoming a well-recognized entity. However, the diagnosis can be easily missed early in the disease course. We report here adult respiratory distress syndrome (ARDS) in a 54-year-old man found to have salicylate toxicity one day after admission to the alcohol detoxification service at a community hospital. He had been taking one enteric-coated aspirin tablet twice a day for more than one year. He also had a 40 pack-year history of cigarette smoking. The list in any standard medical text of factors triggering ARDS is quite lengthy. Over the past few years, salicylate toxicity has been added to this list. As the case reported here illustrates, it is most important that salicylate toxicity be considered in the differential diagnosis for any patient with acute onset of pulmonary edema and normal cardiac function.

III. Segregation of Active Constituents from Tablet Formulations During Grinding: Effects on Coated Tablet Formulations

AbstractAbstractGrinding or milling coated tablets in preparation for their assay can cause the physical separation of an active ingredient from the coating and other tablet components. This phenomenon has been shown to partially account for the poor reproducibility between duplicate assays, and for discrepancies among assays for the same group of tablets but which were composited by different methods.The effect of compositing methods on the assay results is shown with commercial enteric coated aspirin tablets from various manufacturers. Samples for assay were prepared by manual grinding with a glass mortar and pestle, mechanical grinding with an electric tablet grinder, direct dissolution of the tablets in a suitable solvent, and uncoating of the tablets with an organic solvent prior to their manual grinding.Suggestions are offered to minimize the effects of segregation of an active tablet ingredient during grinding or milling on the assay results.

Dissolution Behavior of Commercial Enteric-coated Aspirin Tablets

Dissolution behavior was studied for four commercial batches of enteric-coated aspirin tablets from two companies. The USP XIX dissolution procedure was modified by including pretreatment in simulated gastric juice. The effects of five pretreatment times were studied. Pretreated tablets yielded higher dissolution profiles and fewer undissolved fractions than nonpretreated tablets. Among pretreatments, 15min was adequate and 60min produced the highest dissolution profiles. None of the pretreatments differed significantly from each other. An F test conducted on the data indicated that Product × was significantly better than Product Y at the p = 0.05 level. Batch C was ranked as the best batch irrespective of pretreatment time, followed by Batch D. Batches A and B were equal, although Batch A appeared to be better than B for the (60-min pretreatment, as indicated by the lower t80% value.

Relief of postpartum uterine cramping with propoxyphene and aspirin

Two propoxyphene salts, the hydrochloride and the napsylate, were administered in equimolar quantities as capsules to women professing postpartum uterine cramping. The doses used were 65 and 130 mg of the hydrochloride and 100 and 200 mg of the napsylate. Enteric-coated aspirin tablets, in doses of 325 and 650 mg, were also included in the study, as were identical-appearing placebo capsules and tablets. Single oral doses consisting of 1 capsule and 2 tablets were given with the double-blind control so that equal numbers of patients were treated with each of the 15 medication combinations. Responses in proportion to the dose followed the administration of propoxyphene and of aspirin. Large doses of both analgesics in combination were associated with responses less than expected from the sums of the responses to these same doses given separately. This phenomenon may result from a plateau effect associated with maximum response. A relationship between dosage and possible side effects was not demonstrated.

Rapid Simultaneous Determination of Salicylic Acid and Aspirin by GC I: Analysis of Synthetic Aspirin—Salicylic Acid Mixtures and of Single-Component Aspirin Tablets

A rapid, sensitive GC method for the simultaneous analysis of salicylic acid and aspirin in admixtures and in single-component acetylsalicylic acid (aspirin) tablets is presented. The procedure involves conversion of the two drugs to their methyl esters with diazomethane in tetrahydrofuran solution and subsequent isothermal elution of the components from a 5% OV-210 on Diatoport S glass column. Quantitation is effected by means of an electronic digital integrator with methyl o-methoxybenzoate as the internal standard. The average total drug recovery of 16 synthetic mixtures was 99.70%, with a standard deviation of ±0.58%, while the mean total recovery using the USP procedure was 99.40 ± 0.68%. When applied to the analysis of commercial single-component compressed and enteric coated aspirin tablets, the proposed technique gave results which were, in the majority of cases, in excellent agreement with the USP values for both aspirin and salicylic acid content. With a few formulations, the salicylic acid content was found to be slightly higher with the GC procedure than with the method described in the USP.

Fecal Blood Loss Produced by Oral and Intravenous Administration of Various Salicylates

Fecal blood loss was measured as previously described· by the Cr. 1 method. Serial 3-day composite collections of feces were made before, during, and after administration of the drugs tested. The subjects were male patients from the Gastroenterology Section of the Veterans Administration Hospital. Most of the patients had peptic ulcer and some had bled recently (within 2 weeks of testing). The drugs tested by oral administration were: plain aspirin tablets, U.S.P., 0.33 gm.; enteric-coated aspirin tablets (Ecotrin), 0.33 gm.; calcium acetylsalicylate carbamide (Calurin), 0.33 gm.; plain sodium salicylate tablets, U.S.P., 0.33 gm.; enteric-coated sodium salicylate tablets (Enseals), 0.33 gm.; solution of sodium salicylate, 1 gm. per 10 ml. (Upjohn); and phenacetin tablets, U.S.P., 0.33 gm. All orally administered drugs were given three times a day, before meals. The drugs tested by intravenous administration were: sodium salicylate solution