| Autor: |
Marquis, R. W., Ward, K. W., Roethke, T., Smith, B. R., Ru, Y., Yamashita, D. S., Tomaszek, T. A., Gorycki, P. D., Cheng, H.-Y., James, I. E., Stroup, G. B., Lark, M. W., Gowen, M., Veber, D. F. |
| Zdroj: |
Molecular Pharmaceutics; January 2004, Vol. 1 Issue: 1 p97-100, 4p |
| Abstrakt: |
Pharmacokinetic evaluation of the potent azepanone-based cathepsin K inhibitor 3 showed that it has an oral bioavailability of 42% in the rat and 4.8% in the monkey. The less than optimal oral bioavailabilities of 3 in the rat and the monkey precluded this analogue from being subjected to more detailed pharmacokinetic and pharmacodynamic analyses. In vitro and in vivo studies aimed at identifying the mechanisms which may be limiting the bioavailability of 3 in these species served to guide the syntheses of subsequent analogues for further evaluation. These studies have led to the identification of azepanone 6 that possesses improved oral bioavailability in both the rat (66.3%) and the monkey (23.4%). |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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