Unfortunately, researchers at Eli Lilly were unable to separate satisfactorily the antibacterial and toxic effects of daptomycin. Eli Lilly closed their daptomycin research program. Another company, Cubist, expressed interest in reviving the project. Eli Lilly then entered an agreement with Cubist, and Cubist started its own research program in daptomycin in 1997. This type of arrangement is common between drug companies. Large companies often have more potential projects than available resources. Projects that are not making progress will be shelved to free resources for more promising ones. Partnering with another company allows more projects to be in development. If the shared project is successful, then both companies will share in the profits. The drug discovery group at Cubist pursued a once daily dosing regimen for daptomycin. Instead of minimizing the peak Cp values of daptomycin with twice daily dosing, Cubist's approach emphasized the deeper Cp troughs of a once daily dosing. Cubist found that the muscle toxicity effects could be minimized without sacrificing antibacterial activity. One possible interpretation is that the deeper dips in Cp in the once daily regimen allow the muscles to recover periodically from the toxic effects of the drug. Cubist obtained a patent on their specific and novel dosing schedule which was counter to the prevailing logic on daptomycin. Even though the composition of matter patent on daptomycin has expired, generic manufacturers have been excluded from the market because of Cubist's dosing patent. The case of daptomycin demonstrates how each drug brings its unique challenges to drug discovery. The therapeutic and toxic levels of each drug create new issues that must be addressed by medicinal chemists. OPTIONAL‐Please participate in the online discussion forum.
7.8 CL and Vd Revisited CL vs. Vd plots video Please watch the online video (7 minutes, 27 seconds). A condensed summary of this video can be found in the Video summary page. OPTIONAL‐Please participate in the online discussion forum.