SOFT AND DISSOCIATIVE STEROIDS: A NEW APPROACH FOR THE TREATMENT OF INFLAMMATORY AIRWAY AND EYE DISEASESAbstract
Glucocorticosteroids (GCs) are commonly used for long-term medication in immunosuppressive and anti-inflammatory therapy, but prolonged use of GCs produce number of systemic side effects. To further improve the therapeutic index, that is the ratio of the toxic to the therapeutic dose of a drug, it is at least theoretically possible by changing both pharmacokinetics and pharmacodynamic parameters. Pharmacokinetics can deliberately be altered by using the “inactive metabolite approach” in which one can design a soft analog of a drug that is active at the site of action (e.g.,in the lung in case of inhaled medications) but undergoes a one-step predicted metabolism in the circulation and will be transformed to the very inactive metabolite from which its creation had been started. This process happens after the drug achieves its therapeutic role at the site of action and thus prevents the rest of the body to be exposed to the active drug or to various active or reactive metabolic products. Pharmacodynamic possibility to separate beneficial and deleterious effects of steroids is to try to dissociate the two main activities of glucocorticoids, which are transactivation and transrepression.
Nirav P. Chandegara* and Mehul R. Chorawala
Department of Pharmacology, K. B. Institute of Pharmaceutical Education and Research, Gh-6, Sector-23, Gandhinagar-382023, Gujarat, India
21 September, 2011
07 November, 2011
17 January, 2012