Effects of very low dose and enteric-coated acetylsalicylic acid on prostacyclin and thromboxane formation and on bleeding time in healthy subjects

1998 ◽  
Vol 54 (9-10) ◽  
pp. 707-714 ◽  
Author(s):  
S. M. Bode-Böger ◽  
R. H. Böger ◽  
M. Schubert ◽  
J. C. Frölich
Keyword(s):  
Acetylsalicylic Acid ◽  
Healthy Subjects ◽  
Low Dose ◽  
Bleeding Time ◽  
Enteric Coated ◽  
Thromboxane Formation

Investigation of the Interaction of Blood Platelets with the Coagulation System at the Site of Plug Formation In Vivo in Man - Effect of Low-Dose Aspirin

1987 ◽  
Vol 57 (01) ◽  
pp. 062-066 ◽  
Author(s):  
P A Kyrle ◽  
J Westwick ◽  
M F Scully ◽  
V V Kakkar ◽  
G P Lewis
Keyword(s):  
Platelet Activation ◽  
Thrombin Generation ◽  
Low Dose ◽  
Bleeding Time ◽  
Blood Platelets ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Plug Formation ◽  
Granule Release

SummaryIn 7 healthy volunteers, formation of thrombin (represented by fibrinopeptide A (FPA) generation, α-granule release (represented by β-thromboglobulin [βTG] release) and the generation of thromboxane B2 (TxB2) were measured in vivo in blood emerging from a template bleeding time incision. At the site of plug formation, considerable platelet activation and thrombin generation were seen within the first minute, as indicated by a 110-fold, 50-fold and 30-fold increase of FPA, TxB2 and PTG over the corresponding plasma values. After a further increase of the markers in the subsequent 3 minutes, they reached a plateau during the fourth and fifth minute. A low-dose aspirin regimen (0.42 mg.kg-1.day-1 for 7 days) caused >90% inhibition of TxB2formation in both bleeding time blood and clotted blood. At the site of plug formation, a-granule release was substantially reduced within the first three minutes and thrombin generation was similarly inhibited. We conclude that (a) marked platelet activation and considerable thrombin generation occur in the early stages.of haemostasis, (b) α-granule release in vivo is partially dependent upon cyclo-oxygenase-controlled mechanisms and (c) thrombin generation at the site of plug formation is promoted by the activation of platelets.

Benefit/Risk Profile of Combined Antiplatelet Therapy with Ticlopidine and Aspirin

1991 ◽  
Vol 65 (05) ◽  
pp. 504-510 ◽  
Author(s):  
Raffaele De Caterina ◽  
Rosa Sicari ◽  
Walter Bernini ◽  
Guido Lazzerini ◽  
Giuliana Buti Strata ◽  
...  
Keyword(s):  
Platelet Function ◽  
Low Dose ◽  
Bleeding Time ◽  
Ex Vivo ◽  
Stable Coronary Artery Disease ◽  
High Dose ◽  
Single Drug ◽  
Before And After ◽  
Serum Thromboxane ◽  
Artery Disease

SummaryTiclopidine (T) and aspirin (ASA) are two antiplatelet drugs both capable of prolonging bleeding time (BT), with a different mechanism of action. A synergism in BT prolongation has been reported and is currently considered an argument for not recommending their combination. However, a profound suppression of platelet function might be a desirable counterpart of a marked prolongation of BT, with a possible use in selected clinical situations. We therefore studied ex vivo platelet function (aggregation by ADP 0.5-1-2.5 μM; adrenaline 0.75-2.5 μM; collagen 1.5-150 μg/ml; arachidonic acid 1 mM; PAF 1 μM; adrenaline 0.17 μM + ADP 0.62 μM; serum thromboxane ([TX]B2 generation) and BT (Mielke) in 6 patients with stable coronary artery disease receiving such combination. Patients underwent sequential laboratory evaluations at baseline, after 7 days of T 250 mg b.i.d., before and after the intravenous administration of ASA 500 mg, respectively, and, finally, after a minimum of 7 days of sole ASA oral administration (50 mg/day). The experimental design, therefore, allowed a comparison of T and ASA effects (2nd and 4th evaluation), and an assessment of the combination effect (3rd evaluation). Platelet aggregation in response to all doses of ADP was depressed more by T than by ASA. Conversely, responses to adrenaline, and arachidonate were affected more by ASA than by T. For all other agents, differences were not significant. T + ASA combination was more effective (p <0.05) than either treatment alone in depressing responses to high-dose collagen (% over control, mean ± SEM: T: 95 ± 3; ASA: 96 ± 5; T + ASA: 89 ± 4). Serum TXB2 (basal, ng/ml: 380 ± 54) did not change with T (372 ± 36), dropped to <1 ng/ml on ASA injection and slightly re-increased to 9.1 ± 3.1 ng/ml on oral low-dose ASA. BT (basal 7.4 ± 0.6 min) was affected similarly by T (9.2 ± 0.8) or ASA (9.7 ± 0.9) alone, but increased to 15.0 ± 0.7 min on combination treatment (106% increase over control). Thus, the strong synergism in BT prolongation by ASA-T combination has a counterpart in the inhibition of platelet function in response to strong stimuli such as high-dose collagen, not otherwise affected significantly by single-drug treatment. This effect is a possible rationale for the clinical evaluation of T + ASA combination.

scholarly journals Validation of an HPLC Assay Method for Routine QC Testing and Stability Study of Compounded Low-Dose Capsules of Acetylsalicylic Acid

2018 ◽  
Vol 3 (4) ◽  
pp. 199-206
Author(s):  
Nelly Lonca ◽  
Fabienne Maillard ◽  
Géraldine Leguelinel ◽  
Tahmer Sharkawi ◽  
Ian Soulairol
Keyword(s):  
Acetylsalicylic Acid ◽  
Orthophosphoric Acid ◽  
Low Dose ◽  
Stability Study ◽  
Assay Method ◽  
Stability Studies ◽  
Physicochemical Stability ◽  
Hospital Pharmacies ◽  
Provocation Testing ◽  
Low Dosage

Abstract Background The intolerance to Acetylsalicylic Acid (ASA) can be detected by conducting oral provocation testing (OPT), which is to gradually introduce low doses of ASA. To perform this test, hospital pharmacies compound small batches of different low-dosage ASA capsules. This work aims to validate a method for fast HPLC-UV assay that allows routine quality control and physicochemical stability studies of capsules. Methods The chromatographic separation is performed using a C18 column Kinetex (100 A, 50×4.6 mm, 2.6 µm) equipped with a precolumn C18. Separation is achieved using a mobile phase composed of water-acetonitrile-orthophosphoric acid (68:32:0.2 v/v/v) at a flow rate of 0.8 mL/min and UV detection at 237 nm. Results Validation shows that the method was suitable for routine analysis and could be used to perform stability studies. Conclusions The 5, 25, 100 and 250 mg dosed capsules show acceptable stability over 12 months, while the 1 mg dosed capsule show an unacceptable degradation of more than 15 % after 3 months. Therefore, hospital pharmacy can plan the manufacture of capsules and anticipate the requests of doctors.

Reduced Hemodynamic Responses to Physical and Mental Stress Under Low-Dose Rilmenidine in Healthy Subjects

2006 ◽  
Vol 20 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Renata Rodrigues Teixeira de Castro ◽  
Eduardo Tibiriçá ◽  
Marcos Aurélio Brazão de Oliveira ◽  
Paula Barbosa Baptista Moreira ◽  
Marcelo Flores Catelli ◽  
...  
Keyword(s):  
Mental Stress ◽  
Healthy Subjects ◽  
Low Dose ◽  
Hemodynamic Responses

Template bleeding time after ingestion of ultra low dosages of acetyl salicylic acid in healthy subjects. Preliminary study

1987 ◽  
Vol 48 (4) ◽  
pp. 501-504 ◽  
Author(s):  
C. Doutremepuich ◽  
D. Pailley ◽  
M.C. Anne ◽  
O. de Séze ◽  
J. Paccalin ◽  
...  
Keyword(s):  
Salicylic Acid ◽  
Healthy Subjects ◽  
Bleeding Time ◽  
Acetyl Salicylic Acid ◽  
Preliminary Study
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