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Have there been trials to establish the lowest effective antiplatelet dose
of aspirin? The standard dose of aspirin for antiplatelet effects is 100
mg, available in an enteric coated form. Even this low dose may cause
gastric problems in susceptible people. A lower dose, say 50 mg, may be
just as effective, and I am seeking evidence of this. However, lower doses
do not seem to be available in an enteric coated form, but perhaps this
does not matter for such a low dose.
Advice on this would be appreciated.
Stuart McLean
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[A few replies - db]
From: "Garg, Varun"
To: "'PharmPK.-a-.pharm.cpb.uokhsc.edu'"
Subject: RE: PharmPK Lowest antiplatelet dose of aspirin
Date: Wed, 1 Apr 1998 14:41:47 -0500
MIME-Version: 1.0
The following article appeared in Cardovascular Drugs and Therapy, 1996;
10:727-734:
"The Case for Low-Dose Aspirin for the Prevention of Myocardial Infarction:
But How Low is Low."
Authors: W. Forster and J.R. Parratt.
Conclusion: 30 mg daily is sufficient.
--
Varun Garg, Ph.D.
Otsuka America Pharmaceutical, Inc.
2440 Research Blvd.
Rockville, MD 20850
Ph: (301)-527-4609
fax: (301)-721-7009
email: varung.-a-.mocr.oapi.com
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From: DebHolton
Date: Wed, 1 Apr 1998 15:06:09 EST
To: PharmPK.aaa.pharm.cpb.uokhsc.edu
Mime-Version: 1.0
Subject: Re: PharmPK Lowest antiplatelet dose of aspirin
Mayor Pharmaceutical Laboratories out of Phoenix, Arizona offers many products
in oral spray form for buccal absorption. I do not know if aspirin is
available yet, but they do carry many over the counter products in spray form.
The dosages are relatively low because of the more efficient buccal absorption
vai their microfine sprays. For example, a full dose of acetaminophen is 4mg
vs. 500mg in one extra strength Tylenol, so if they have an aspirin product,
it may have just the product you are looking for.
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Mime-Version: 1.0
Date: Wed, 1 Apr 1998 18:48:18 -0400
To: PharmPK.at.pharm.cpb.uokhsc.edu
From: "Lawrence H. Block, Ph.D."
Subject: Lowest antiplatelet dose of aspirin
In response to the request for information on the lowest aspirin dose, we
published a paper in 1980 on the antiplatelet effects of aspirin in human
subjects (M. J. Paccioretti and L. H. Block, "Effects of aspirin on
platelet aggregation as a function of dosage and time," Clin. Pharmacol.
Therap. 27: 803-809 (1980).) The lowest dose of aspirin we used was 81 mg.
In our study, single doses of aspirin ranging from 81 to 325 mg were given
perorally to normal healthy volunteers. In vitro platelet aggregation was
determined as a function of time. Based on our data, neither the rate nor
extent of platelet aggregation depended on the size of the dose; i.e. 81 mg
was as effective as 325 mg. The effect persisted for at least 96 hours
post-dosing. The formulation we used was an 81-mg chewable aspirin
tablet. No substantive side effects were evident among the 7 subjects
participating in the study.
Lawrence H. Block, Ph.D.
Professor of Pharmaceutics and Chair
Department of Medicinal Chemistry and
Pharmaceutics
Mylan School of Pharmacy
Duquesne University
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Date: Thu, 02 Apr 1998 08:34:44 +0200
From: "JOAN LOMBARD"
To: PharmPK.-a-.pharm.cpb.uokhsc.edu
Subject: Re: PharmPK Lowest antiplatelet dose of aspirin
Mime-Version: 1.0
Just for what it is worth, in South Africa an enteric coated aspirin
product containing 81mg of aspirin is available, is that not the true
anti-platelet dose?
Joan Lombard
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[A couple of replies - db]
From: "Lands, William"
To: "'PharmPK.at.pharm.cpb.uokhsc.edu'"
Subject: RE: Lowest antiplatelet dose of aspirin
Date: Thu, 2 Apr 1998 10:47:42 -0500
Because - 1)- aspirin irreversibly inhibits its target,
2)- cyclooxygenase, and platelets have no nucleus to permit
creating new enzyme,
3)- platelets require more than a week to be replaced with new
platelets,
the low-dose aspirin can be taken every other day or every third day and still
achieve significant anti-thrombosis preventive effect. You might regard that
tactic to be a "dose-lowering" approach to further diminish risk of gastric
injury.
_____________________________________
Bill Lands
Voice = (301) 443-0276
FAX = (301) 594-0673
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From: DGarg8838
Date: Thu, 2 Apr 1998 20:20:32 EST
To: PharmPK.at.pharm.cpb.uokhsc.edu
Mime-Version: 1.0
Subject: Re: PharmPK Lowest antiplatelet dose of aspirin
I was at the 1998 ASCPT meeting in New Orleans this week. There was one
abstract at the meeting entitled, "Antiplatelet Effect of Low Dose
Acetylsalicylic Acid: Pharmacokinetic and Pharmacodynamic Analysis. IJ Jang,
KS Yu, YC Yim, SC Shin, Dept of Pharmacology and Clin Pharmacology Unit, Seoul
National University, College of Medicine and Hospital, Seoul, Korea. CPT, 63
(2), Page 223, February 1998.
The abstract indicates that 50, 100 and 300 mg doses were tried. 50 mg dose
inhibited platelet aggregation (50%) only for 3 hours. The other two doses
inhibited platelets for 24 to 48 hours. You may like to contact the authors
for further details.
Dyal Garg
561-737-3954
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Reply-To:
From: "William Loftin" <4003.at.amigo.net>
To:
Subject: Re: PharmPK Lowest antiplatelet dose of aspirin
Date: Fri, 3 Apr 1998 06:43:43 -0700
X-MSMail-Priority: Normal
X-Priority: 3
MIME-Version: 1.0
I have not seen 100 mg EC ASA tablet: also the one prepackeger has stopped
U.D. the EC 81 mg tablets
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[A few replies - db]
Date: Thu, 02 Apr 1998 13:29:05 -0700
From: Patrick Robertson
Reply-To: proberts.aaa.cha.ab.ca
Organization: Capital Health - RAH Site
MIME-Version: 1.0
To: PharmPK.-a-.pharm.cpb.uokhsc.edu
CC: Multiple recipients of PharmPK - Sent by
Subject: Re: PharmPK Lowest antiplatelet dose of aspirin
Hello Stuart,
The lowest dose that I am aware used in clinical trials for platelet inhibition
was 38 mg in the Dutch TIA Trial. (NEJM 1991; 325: 1261-6) This aspirin was
provided as a calcium salt, and 38 mg was reported to be equivalent to 30 mg
asparin. By the way, this was a criticism of this study. It was demonstrated
that there was no significant difference between this dose and conventional
doses (280 mg, apparently in Holland). With regards to tolerability, I beleive
it was the TASS trial that demonstrated that there was no difference between
report GI adverse effects of ASA 325mg and placebo. There was a very high
background in the placebo group; approximately 30% report GI disturbances with
placebo (lactose intolerance???)
Thanks
Patrick Robertson, Pharm.D.
Emonton, Alberta, Canada
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X-Sender: rjmeyer.at.globaldialog.com
Date: Fri, 03 Apr 1998 17:48:14 -0600
To: PharmPK.aaa.pharm.cpb.uokhsc.edu
From: Bob Meyer
Subject: Re: PharmPK Lowest antiplatelet dose of aspirin
Mime-Version: 1.0
Actually, aspirin is available as 81mg in the low-dose form (same as the
old-time children's strength), and is available in an enteric-coated form.
Bob Meyer, RPh
rjmeyer.at.globaldialog.com
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