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CNS Drug Development, Lessons Learned, Part 5

How Preclinical and Human Safety Studies Inform the Approval and Subsequent Use of a New Drug—Suvorexant as an Example


Journal of Psychiatric Practice®: March 2018 - Volume 24 - Issue 2 - p 104–110
doi: 10.1097/PRA.0000000000000295

This column is the fifth in a series examining the advances being made in central nervous system drug development because of advances in molecular pharmacology and an improved understanding of the neurobiology underlying disturbances in brain function including psychiatric illnesses. This column covers the special animal and human studies conducted as part of the development of suvorexant, which is the first in the class of dual orexin 1 and 2 receptor antagonists to be approved; it has an indication for the treatment of disturbances in sleep onset and maintenance. The animal studies included determination of the therapeutic index of the drug (ie, lethal dose 50 which is the dose at which 50% of animals die following administration of the drug), adverse effects on fertility, teratogenicity, carcinogenicity, and ability to cause narcolepsy. The human studies included investigation of the effects of the drug on balance, memory, driving performance, and propensity to cause respiratory depression in normal volunteers and individuals with mild to moderate chronic obstructive pulmonary disorder or mild to moderate obstructive sleep apnea. This column illustrates how targeting the drug to one mechanism out of hundreds yields increased safety and highlights the importance of the package insert which summarizes the results of all of the studies from the drug’s development program.

PRESKORN: Kansas University School of Medicine-Wichita, Wichita, KS

S.H.P. has worked with over 135 pharmaceutical companies in the United States and throughout the world. Over the past year, he has received grants/research support from or has served as a consultant, on the advisory board, or on the speaker’s bureau for Alkermes, Allergan, Bionomics, BioXcel, Cercor, Food and Drug Administration, Janssen, National Institute of Mental Health, Merck, Novaritis, Pfizer, Rugen Holdings, and Sunovion.

Please send correspondence to: Sheldon H. Preskorn, MD, University of Kansas Medical Center, 1010 N. Kansas, Wichita, KS 67217.

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