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Abstract

The aim of this study was to assess the pharmacological effects of aspirin on prostanoid biosynthesis -as measured by plasma thromboxane B 2 (TXB 2 ) and prostaglandin E 2 (PGE 2 ) 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 TXB 2 and PGE 2 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.Faecal porphyrins, in volunteers dosed with aspirin for 5 days, were increased by 195% compared with placebo (P50.01); plasma TXB 2 and PGE 2 concentrations were reduced by 499% in volunteers dosed with aspirin for 5 days compared with placebo (both P50.001); PAH clearance was significantly (P50.045) lower in volunteers dosed with aspirin, 150 minutes after the start of infusion on day 5 of the treatment period; creatinine clearance was unaffected by aspirin treatment.Faecal porphyrins, plasma prostanoid concentrations and PAH clearance offer sensitive markers for assessment of non-steroidal anti-inflammatory drug (NSAID) mechanistics in the clinical environment.