Pharmacokinetics and pharmacodynamics of tepoxalin after single oral dose administration to healthy volunteers.
Publication/Presentation Date
5-1-1996
Abstract
This study was conducted to examine the pharmacokinetics and pharmacodynamics of tepoxalin in healthy volunteers, an antiinflammatory compound that inhibits cyclooxygenase and lipoxygenase. Tepoxalin was absorbed after oral administration of single doses from 35 to 300 mg, after which it was rapidly converted to an acidic metabolite, RWJ 20142, which inhibits cyclooxygenase but not lipoxygenase. The areas under the concentration-time curve (AUC) of tepoxalin and RWJ 20142 in plasma increased in a dose-dependent fashion. Administration of the lowest dose of tepoxalin completely inhibited whole blood cyclooxygenase for the entire period of observation. This inhibition correlated closely with that of secretion and aggregation induced by collagen of platelets obtained from these subjects. Similarly, administration of tepoxalin was associated with significant inhibition of lipoxygenase in whole blood. Lipoxygenase was inhibited a maximum of 60% in a time-dependent fashion, and the duration of inhibition was dose-dependent. These studies demonstrate that tepoxalin inhibits whole blood cyclooxygenase, lipoxygenase, and platelet function after oral administration in humans.
Volume
36
Issue
5
First Page
462
Last Page
468
ISSN
0091-2700
Published In/Presented At
Waldman, S. A., Vitow, C., Osborne, B., Gillen, L., Argentieri, D. C., Wong, F. A., Smith, I. L., Chow, A. T., Misiti, J., & Bjornsson, T. D. (1996). Pharmacokinetics and pharmacodynamics of tepoxalin after single oral dose administration to healthy volunteers. Journal of clinical pharmacology, 36(5), 462–468. https://doi.org/10.1002/j.1552-4604.1996.tb05033.x
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
8739025
Department(s)
Administration and Leadership
Document Type
Article