Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers

Abstract

BackgroundThe pharmacology of single doses of acetylsalicylic acid (ASA) administered intravenously (250 or 500 mg) or orally (100, 300, or 500 mg) was evaluated in a randomized, placebo-controlled, crossover study.MethodsBlood and urine samples were collected before and up to 24 hours after administration of ASA in 22 healthy volunteers. Pharmacokinetic parameters and measurements of platelet aggregation were determined using validated techniques.ResultsA comparison between administration routes showed that the geometric mean dose-corrected peak concentrations (Cmax/D) and the geometric mean dose-corrected area under the curve (AUC0–∞/D) were higher following intravenous administration of ASA 500 mg compared with oral administration (estimated ratios were 11.23 and 2.03, respectively). Complete inhibition of platelet aggregation was achieved within 5 minutes with both intravenous ASA doses, reflecting a rapid onset of inhibition that was not observed with oral dosing. At 5 minutes after administration, the mean reduction in arachidonic acid-induced thromboxane B2 synthesis ex vivo was 99.3% with ASA 250 mg intravenously and 99.7% with ASA 500 mg intravenously. In exploratory analyses, thromboxane B2 synthesis was significantly lower after intravenous versus oral ASA 500 mg (P<0.0001) at each observed time point up to the first hour after administration. Concentrations of 6-keto-prostaglandin1α at 5 and 20 minutes after dosing were also significantly lower with ASA 500 mg intravenously than with ASA 500 mg orally.ConclusionThis study demonstrates that intravenous ASA provides more rapid and consistent platelet inhibition than oral ASA within the first hour after dosing.

Acetyl salicylic acid attenuates cardiac hypertrophy through Wnt signaling

“…The results were observed in aspirin within its "antiplatelet" dosage range [22,23,25,33]. Our findings strongly suggested that aside from its anti-thrombotic properties, aspirin confers cardiovascular benefits via the attenuation of VH.…”

“…However, published pharmacokinetics studies on this aspirin dose have revealed contradictory C max depending on formulation, such as soluble, rapid-release, or chewable 100 mg tablets exhibiting minor differences [22,23,33]; by contrast, the enteric or controlled release tablets showed wide and significant variations [37,38]. Our in vitro results simulated human plasma levels based on 100 mg rapid-acting aspirin formulations (soluble and rapid-release tablets), whose quick action is desirable during the acute onset of symptoms, such as in MI.…”

Effects of Aspirin on Endothelial Function and Hypertension

“…These doses do not inhibition of COX-2 with COX-1 inhibition being the net pharmacological effect [8, 15]. Because of irreversible action of aspirin (i.e.…”

Microfludic platforms for the evaluation of anti-platelet agent efficacy under hyper-shear conditions associated with ventricular assist devices

“…For both ASA and ticagrelor, two different final concentrations in GFP were tested: 125 and 250 μM for ASA and 250 and 500 nM for ticagrelor. The lower values were chosen to replicate typical in vivo therapeutic doses, as detected in plasma after administration of commercial tablets of ASA (500 mg) and ticagrelor (90 mg) in humans [38,39]. Higher concentration levels were chosen to replicate conditions tested in previous in vitro studies [40,41], and also to emulate higher doses of drugs in vivo .…”