A trial to assess the clinical mechanistics of aspirin in healthy volunteers

Abstract

The aim of this study was to assess the pharmacological effects of aspirin on prostanoid biosynthesis — as measured by plasma thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) concentrations — and two physiological functions thought to be mediated via prostanoids, namely gastrointestinal mucosal integrity — as measured by faecal porphyrins — and renal blood flow — as measured by para-aminohippuric acid (PAH) and creatinine clearance. The trial was a randomized, double-blind, placebo-controlled crossover design, with each volunteer taking 750 mg aspirin (British Pharmacopoeia) or placebo, three times a day for 5 days, with an 18-day washout period between treatments. Faecal porphyrins were measured before the first dose and on days 2 to 5 inclusive of each dosing period; plasma TXB2 and PGE2 concentrations were measured before dosing and 0.5 hours after the final dose on day 5 of each of the dosing periods; PAH clearance was measured before dosing and at 90, 120 and 150 min after the start of the infusion of PAH on day 1 and day 5 of each dosing period; creatinine clearance was measured before dosing and prior to the final dose on day 5 of each dosing period.