Preserving AntiPlatelet Activity of Aspirin

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Preserving Anti-Platelet Activity of Aspirin by
Preventing Hydrolysis John C. Somberg, Vasant
V. Ranade, Imran Qadeer, Jackie Coleman,
Janos Molnar Rush University, Chicago,
IL Accumetrics, San Diego, CA Academic
Pharmaceuticals, Lake Bluff, IL
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Purpose of the Study Hydrolysis of aspirin
markedly reduces the anti-platelet activity of
aspirin (ASA) preventing the development of an
effective IV formulation. This study evaluates a
new IV formulation that prevents hydrolysis and
preserves platelet inhibition.
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Benefits of ASAISIS-2 Second International
Study of Infarct Survival

Reduction in odds of vascular death in days 035,
by time from pain onset
01
2
3
4
Subtotal for 04
512
1324
Subtotal for 524
Total for 024
0.5
1.0
1.5
0.5
1.0
1.5
Odds ratio and 95CI
The ISIS-2 collaborative group.
Lancet 1988 ii 34960.
SK Streptokinase
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Benefits of ASA
Kong et al, AJC 90622, 2002
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Feldman and Cryer, AJC 84 404, 1999
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Kotake et al. JCPT 31237, 2006
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• Methods
• Hydrolysis was determined by HPLC using a Luna
  column (5µ, 100x46 mm), a constant flow pump
  (Thermo-Finnigan Spectra System P2000) and a
  Spectra 200 programmable UV wavelength detector.
• Platelet function was evaluated ex vivo using
  the Verify Now assay developed by Accumetrics
  that employs a method that is based upon the
  principle that agonist (arachidonic acid)
  -induced activated platelets bind to
  fibrinogen-coated polystyrene beads that
  agglutinate in whole-blood. Infrared-light
  transmittance through the chamber increases as
  the agglutinated platelets and beads fall out of
  the solution.

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Rate of Hydrolysis Percent not
hydrolyzed Fresh 1 Day 1 month
6 months 40C 40C
40 C New formulation ASA 99.8
99 99 99 Aqueous ASA
97.9 70 56 11
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The Effect of ASA Solutions on Platelet
Inhibition Percent Inhibition
Platelets Fresh 1 month 6
months Aqueous ASA 26 0
0 New ASA Formulation 37 37
39 Vehicle Solution 0 0
0
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• Conclusions
• Aqueous solutions of ASA hydrolyzes and this
  correlates with a diminished ex vivo ASA effect
  on platelet function
• A new formulation of ASA for IV administration
  shows no hydrolysis at 1 6 months of storage
  at 40C
• This lack of hydrolysis of the new formulation
  correlates with ex vivo measured platelet
  inhibition by ASA
• Availability of an IV formulation of ASA may
  be useful in the treatment of acute coronary
  syndromes