Abstract:
:The purpose of this study was to develop quantitative structure-activity/pharmacokinetic relationships (QSAR/QSPKR) for 11 selected corticosteroids in man. Multiple linear regression analysis with an automatic forward step-wise inclusion algorithm was used to construct QSAR/QSPKR models from molecular and submolecular descriptors that were generated using the SYBYL and KowWin computer programs. The final equations describing steroid relative receptor affinity, systemic clearance, volume of distribution, fraction unbound in plasma, and percent of oral absorption, all showed significant correlations (R(2) range 0.841 to 0.977). These relationships were crossvalidated using the leave-one-out method, and appeared to have good predictive performance (Q(2) range 0.715 to 0.912). In addition, a general method for integrating QSAR/QSPKR data to predict the time course of pharmacologic effects is presented. This approach, termed quantitative structure-pharmacodynamic relationships modeling, was successfully applied to predict the rapid cortisol suppressive effects of triamcinolone acetonide after a 2-mg intravenous bolus dose in healthy volunteers.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Mager DE,Jusko WJdoi
10.1002/jps.10231subject
Has Abstractpub_date
2002-11-01 00:00:00pages
2441-51issue
11eissn
0022-3549issn
1520-6017pii
S0022-3549(16)31112-1journal_volume
91pub_type
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