What are the Different Generations of P-Glycoprotein Inhibitors?
First-Generation Inhibitors These were initially identified as non-specific agents that inhibited P-gp. Examples include verapamil and cyclosporine A. However, their use is limited due to significant side effects and interactions with other drugs.
Second-Generation Inhibitors These inhibitors are more selective for P-gp and have fewer side effects compared to first-generation inhibitors. Examples include valspodar (PSC-833) and tariquidar (XR9576). Despite improved specificity, their clinical success has been limited.
Third-Generation Inhibitors These are highly specific and potent P-gp inhibitors with minimal side effects. Examples include zosuquidar (LY335979) and elacridar (GF120918). These inhibitors are currently being evaluated in clinical trials.
