The Pharmacokinetics of Salicylic Acid Following Single and Repeated Administration of Slow-release Formulations of Aspirin in Healthy Japanese Volunteers and the Effect of Dosing Time

The effect of dosing time on salicylic acid (SA) kinetics after single oral administrations of two different aspirin formulations, a slow-release tablet (Veri®) and enteric-coated granules (Minimax®), was investigated in 15 healthy Japanese men. Eight subjects received slow-release tablets and the other seven subjects received enteric-coated granules. Each aspirin formulation was given in the morning (8: 30) or in the evening (20: 30) in a randomly assigned cross-over study. After the single dose study, the SA kinetics following repeated administration of the two different aspirin formulations, 2600 mg daily for five days, was investigated. Eight subjects received the slow-release tablets, and one subject received the enteric-coated granules. No time dependent changes were observed in SA kinetics after single and repeated administra tions of the two different formulations. In both dosing times, the mean peak SA concentrations in plasma were significantly higher in the enteric-coated granules, the mean elimination half-lives of plasma SA were significantly longer in the slow-release tablets, and the mean areas under the curves were significantly larger in the enteric coated granules. In repeated administration of the slow-release tablets, the mean SA concentrations were 47.4 ± 21.9 μ g/ml after administration at 20: 30 and 44.7 ± 24.4μ g/ml after dosing at 8: 30 on the day 5. The plateau SA concentrations in plasma were attained after day 3 to day 4, but after the day 5 SA concentrations in plasma tended to be decreased. This may be due to enzyme induction in the salicylate metabolism.