Pharmacokinetic and Pharmacodynamic Profile of a Novel Phospholipid Aspirin Formulation

Figures

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  Fig. 1. Structure of aspirin.

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  Fig. 2. Mechanism of action of aspirin and COX inhibition. Prostaglandins (thromboxane and prostacyclin) are produced from arachidonic acid via the action of the COX-1 and COX-2 enzymes. Aspirin blocks both of these pathways by acetylating the COX enzyme. COX cyclooxygenase, ADP adenosine diphosphate

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  Fig. 3. Mechanism of gastric injury. The graphic depicts the gastric epithelial layer, with its normal hydrophobic layer that protects against acid injury. When the phospholipid layer is disrupted, the protective mechanism is compromised, allowing acid diffusion and injury to the epithelial layer. NSAIDs non-steroidal anti-inflammatory drugs

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  Fig. 4. Mechanism of action of PL-ASA. (1) In the stomach, the PL-ASA capsule rapidly dissolves, releasing the liquid lipid-aspirin complex. (2) In the duodenum, the rising pH leads to dissociation of the lipid-aspirin complex. (3) The aspirin is now free for absorption. Data from in vitro experiments, data on file, PLx Pharma. PL-ASA phospholipid-aspirin complex

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  Fig. 5. Pharmacokinetic bioequivalence study of PL-ASA and IR (plain) aspirin. Values over time of acetylsalicylic acid and salicylic acid in plasma after a single dose of 325 or 650 mg of PL-ASA. Source: Angiolillo et al. [48]. PL-ASA phospholipid-aspirin complex, IR-ASA immediate-release aspirin

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  Fig. 6. Pharmacokinetics of plain aspirin, enteric-coated aspirin, and PL-ASA. Values over time of acetylsalicylic acid in plasma for plain aspirin, PL-ASA, and enteric-coated aspirin. P-values for the comparison at each time point of pharmacokinetic curves were calculated by using the ‘p value from the two-sample Student’s t test. Source: Bhatt et al. [10]. EC enteric-coated. PL-ASA phospholipid-aspirin complex

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  Fig. 7. Time to complete TxB2 inhibition. PL-ASA and plain aspirin had faster times to >99% inhibition of TxB2 formation compared with enteric-coated aspirin. P-values were calculated using a mixed-effects model. In the event a given patient did not reach the 99% inhibition within 72 h after the initial dose, time to 99% inhibition was imputed as 72 h. Source: Bhatt et al. [10]. PL-ASA phospholipid-aspirin complex, TxB2 thromboxane B2, EC enteric-coated, LS least squares

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  Fig. 8. Individual TxB2 inhibition over time. Percentage inhibition of serum TxB2 concentration over baseline after dosing with plain aspirin, PL-ASA, and EC-ASA. Blue lines represent the percentage inhibition in individual patients who reached 99% inhibition by 72 h after the first dose of study drug. Orange lines represent the percentage inhibition in individual patients who did not reach 99% inhibition by 72 h after the first dose of study drug. The horizontal line designates 99% inhibition. Source: Bhatt et al. [10]. PL-ASA phospholipid-aspirin complex, TxB2 thromboxane B2, EC-ASA enteric-coated aspirin