Table 2.

Summary of clinical studies in which dose-dependent effects of aspirin on prostanoid production were evaluated

Study design	Aspirin dose(s)	Treatment time	Prostanoid measurements	Effect	Reference
Healthy volunteers (n = 5)	20, 40, 80, 160, 325 and 650 mg day−1, and 650 mg twice and four times daily	Each dose taken for 7 days in ascending order in consecutive weeks	Urine 2,3-dinor-TXB2	Dose-dependent reduction in 2,3-dinor-TXB2 and PGI-M concentrations using aspirin between 20 and 325 mg day−1	[1]
			Urine PGI-M
Healthy volunteers (n = 8)	20 and 100 mg given to the same volunteers	Each dose given once with a 2-week washout period between doses	TXB2 and 6-keto- PGF1α formation during blood clotting	Dose-dependent inhibition of PGI2 production	[93]
Healthy volunteers (n = 5)	150 and 300 mg	Once	Platelet TXB2 production PGI2 production in vein segments	Inhibition of TXB2 and PGI2 production by both doses	[89]
Randomized parallel study in healthy volunteers (n = 52)	80 and 325 mg day−1 or 325 mg enteric coated aspirin	Daily or every other day dosing for 14 days	TXB2 and 6-keto-PGF1α in blood	PGI2 production inhibited by 325 mg only	[95]
Placebo-controlled trial in healthy volunteers (n = 45)	75 and 162.5 mg day−1; 325 mg every second day; 75 mg controlled release aspirin day−1	4 days	PGI2 synthesis following i.v. infusion of bradykinin	All doses of standard aspirin suppressed bradykinin-stimulated PGI2	[87]
Double-blind trial using healthy volunteers (n = 45)	162.5 mg day−1 or 325 mg every second day	28 days	Serum TXB2	Dose-dependent inhibition of PGI-M	[87]
			Urine 2,3-dinor-TXB2
			Urine PGI-M
Single-blind randomized prospective study in healthy volunteers (n = 10)	50 mg p.o. aspirin or 500 mg i.v. infusion over 60 min	Once	Platelet TXB2	Dose-dependent inhibition of urinary metabolites	[96]
			Urine 2,3-dinor-TXB2
			Urine PGI-M
			Urine PGE2
Post-stroke patients (n = 19)	40, 320 and 1280 mg day−1 given in ascending doses	7 weeks; 2-week washout periods between doses	Serum TXB2	Dose-dependent inhibition of urinary metabolites	[94]
			Urine 11-dehydro-TXB2
			Urine PGI-M
Placebo-controlled study in patients with cardiovascular metabolic syndrome (n = 121)	100 and 300 mg day−1	2 weeks	Serum TXB2	Only TXB2 production inhibited	[97]
			Serum 6-keto-PGF1α
Crossover study including patients with type I diabetes (n = 8) and healthy controls (n = 7)	80 mg every second day or 325 mg day−1	14 days with 2-week washout period between treatments	Urine TXB2	80 mg every second day suppressed PGI2 production to a greater extent than 325 mg day−1	[103]
			Urine 6-keto-PGF1α
Patients undergoing aortocoronary bypass surgery (n = 70)	40, 80 or 325 mg	Aspirin administered once 12 to 16 h before surgery	Serum TXB2	Dose-dependent inhibition of TXB2 and PGI2 production	[90]
			PGI2 production by aortic and saphenous vein tissue measured ex vivo
Patients undergoing surgery for varicose veins (n = 47)	40, 81 and 300 mg	14 h pre-operation	PGI2 synthesis from vein sections ex vivo measured by bioassay	81 and 300 mg aspirin significantly inhibited PGI2 synthesis whereas 40 mg had no effect	[88]
Patients undergoing bowel resection (n = 62)	40, 75 or 300 mg	Once, 24 h before operation	6-keto-PGF1α synthesis by mesenteric arteries or veins segments obtained during surgery	Arterial and venous 6-keto-PGF1α synthesis significantly inhibited by all doses	[91]
Placebo-controlled study in subjects with prior sporadic colorectal adenoma(s) (n = 60)	81, 325 and 650 mg day−1	4 weeks	Rectal mucosal PGE2 concentrations at baseline and after 4-week treatment	All doses significantly suppressed PGE2	[137]
Randomized double-blind placebo-controlled crossover study in healthy volunteers (n = 12)	75 and 300 mg day−1 or 300 mg day−1 enteric coated aspirin	Each treatment period for 5 days with 2-week washout period between treatments	TXB2 and PGE2 in rectal dialysates at baseline and after 5 days	TXB2 but not PGE2 concentrations inhibited by all doses	[138]