Minimizing metabolic activation, drug

Approaches for Minimizing Metabolic Activation of New Drug Candidates in Drug Discovery... 

Minimizing Metabolic Activation in Drug Discovery Future Directions. 536... 

Although a major rationale for minimizing metabolic activation during drug discovery is related to the desire to reduce the potential for idiosyncratic toxicities in humans, these efforts can also aid in the interpretation of the preclinical safety... 

Overall, we believe that efforts to minimize metabolic activation during dmg discovery can enhance the overall quality of drug candidates that are advanced into development in a number of respects and result in an increased probabihty of success. 

Kumar S, Mitra K, Kassahun K, Badlie TA. Approaches for minimizing metabolic activation of new drug candidates in drug discovery. Handb Exp Pharmacol 2010 (196) 511-544. 

Zanamivir is delivered directly to the respiratory tract via inhalation. Ten to twenty percent of the active compound reaches the lungs, and the remainder is deposited in the oropharynx. The concentration of the drug in the respiratory tract is estimated to be more than 1000 times the 50% inhibitory concentration for neuraminidase, and the pulmonary half-life is 2.8 hours. Five to fifteen percent of the total dose (10 mg twice daily for 5 days for treatment and 10 mg once daily for prevention) is absorbed and excreted in the urine with minimal metabolism. Potential adverse effects include cough, bronchospasm (occasionally severe), reversible decrease in pulmonary function, and transient nasal and throat discomfort. 

Evans, D. C., and Baillie, T. A. (2005). Minimizing the potential for metabolic activation as an integral part of drug design. Curr. Opin. Drug Discov. Devel. 8 44-50. 

Kalgutkar, A. S., Soglia, J. R. Minimizing the potential for metabolic activation in drug discovery. Expert Opin. Drug Metab. Toxicol. 2005, 7,91-141. 

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