This column illustrates the importance of considering interindividual variance when prescribing medications. In this tragic case, the failure to consider age and body weight when prescribing a drug, imipramine, with a narrow therapeutic index caused the death of an otherwise physically healthy 6-year-old child. This death could also have been avoided by using therapeutic drug monitoring to properly adjust the dose. This case illustrates the importance of the second (pharmacokinetics) and third (biological variance) variables in the equation frequently cited in this column: clinical response=affinity for and intrinsic activity at site of action x drug concentration at site of action x underlying biology of the patient. (Journal of Psychiatric Practice 2011;17:118–123)
Department of Psychiatry, University of Kansas School of Medicine-Wichita, and Chief Science Officer and Medical Director, Clinical Research Institute, Wichita, Kansas.
Adapted from Preskorn SH. What happened to Tommy? Journal of Practical Psychiatry and Behavioral Health 1998;4:363–7.
Disclosure statement: Within the last 12 months, Dr. Preskorn, as chief science officer of the Clinical Research Institute, Wichita, KS, and, in many cases, as principal investigator, has received grants/research support from or has served as a consultant for, on the advisory board, or on the speakers bureau for the following entities: Abbott, Allergan, Biovail, Boehringer Ingelheim, Bristol-Myers-Squibb, Eisai, Eli Lilly, Evotec, Ipsen, Johnson & Johnson, Labopharma, Link Medicine, Merck, NovaDel Pharma, Orexigen, Prexa, Psylin, Pfizer, Sunovion, Takeda, and Targacept.
He has more than 30 years of drug development research experience at all levels (i.e., preclinical through Phase IV) and has been a principal investigator on over 300 clinical trials including every antidepressant marketed in the United States over the last 25 years. Dr. Preskorn maintains a website at <www.preskorn.com> where readers can access previous columns and other publications.