Pharmacokinetics of E-6087, a new anti-inflammatory agent, in rats and dogs
Article first published online: 18 DEC 2001
Copyright © 2001 John Wiley & Sons, Ltd.
Biopharmaceutics & Drug Disposition
Volume 22, Issue 6, pages 231–242, September 2001
How to Cite
Reinoso, R. F., Farrán, R., Moragón, T., García-Soret, A. and Martínez, L. (2001), Pharmacokinetics of E-6087, a new anti-inflammatory agent, in rats and dogs. Biopharm. Drug Dispos., 22: 231–242. doi: 10.1002/bdd.258
- Issue published online: 18 DEC 2001
- Article first published online: 18 DEC 2001
- Manuscript Accepted: 22 JUN 2001
- Manuscript Revised: 27 APR 2001
- Manuscript Received: 3 JUL 2000
- anti-inflammatory agents;
The pharmacokinetics of E-6087, a newly developed cyclooxygenase-2 inhibitor, was studied in rats and dogs after single oral and intravenous doses. In both animal species, E-6087 was characterized by a long elimination half-life (20–35 h), a low plasma clearance (0.10–0.22 l h−1 kg−1) and a relatively large volume of distribution (2–6 l kg−1). Oral bioavailability was lower in dogs than in rats whereas a faster elimination was found in rats. Multiple peaks were present regardless of administration route and animal species, suggesting the existence of enterohepatic circulation. Gender effect on the pharmacokinetics of E-6087 was only found in rats, with greater exposure and longer elimination in females than in males. Food intake reduced the bioavailability (∼22%) with no apparent changes in the absorption rate. After oral dosing of 1, 5 and 25 mg kg−1 to rats, linearity was lost at the highest dose due to the low aqueous solubility of E-6087. Drug absorption was improved by micronization. E-6087 and E-6132, (a pharmacologically active metabolite), showed different pharmacokinetics. The higher percentage of E-6087 at early times suggests that E-6087 is the main compound responsible for in vivo activity, although E-6132 would contribute to the activity at later times. Copyright © 2001 John Wiley & Sons, Ltd.