| abstract |
The present invention provides a method of using a physiologically-based pharmacokinetic model to select a prodrug molecule (NO-X) comprising a therapeutic agent X (e.g. nonsteroidal anti-inflammatory drug, (NSAID)) and an appropriate nitric oxide donor NO. The NSAID can be a non-selective or selective cyclooxygenase inhibitor or other biocompatible compound comprising a carboxyl group. The pharmacokinetic model uses in vitro and/or in silico data to estimate an optimal set of parameters that can predict whether a particular NO-X candidate is capable of producing desirable therapeutic effects, e.g. enhanced antiiflammatory activity, reduced intestinal, cardiac and renal toxicity. Accordingly, the present invention may help with proper selection of an appropriate candidate for drug development, with less development time and at lower cost. |