The “atypical” antipsychotics are grouped together based on what they are not (i.e., not dopamine-2 selective antagonists like haloperidol). While sharing this characteristic, these agents differ substantially in pharmacokinetics and pharmacodynamics. The first two columns in this series reviewed the bioavailability, half-life, and metabolism of the 10 newer “atypical” antipsychotics, including the most recently marketed members of this class (asenapine, iloperidone, and lurasidone). This third column in the series discusses the effect hepatic and renal impairment has on the clearance and hence dosing recommendations for these agents. An understanding of the pharmacokinetic differences among the “atypical” antipsychotics discussed in this series of columns can help clinicians optimize drug selection and dose for specific patients under specific treatment conditions. A subsequent column in the series will review the substantial and clinically important pharmacodynamic differences among these agents. (Journal of Psychiatric Practice 2012;18:430–437)
SHELDON H. PRESKORN, MD, is Professor, Department of Psychiatry, University of Kansas School of Medicine-Wichita, and Chief Science Officer and Medical Director, Kansas University- Wichita Clinical Trials Unit (KU-W CTU), Wichita, Kansas. He has more than 35 years of drug development research experience at all levels (i.e., preclinical through Phase IV) and has been a principal investigator on over 350 clinical trials—funded by industry, the federal government, or private foundations—including trials of every antidepressant and antipsychotic medication marketed in the United States over a period of 25 years. That includes every antipsychotic agent discussed in this series of columns. Dr. Preskorn maintains a website at http://www.preskorn.com where readers can access previous columns and other publications.
Disclosure statement: Over his career, Dr. Preskorn has worked with over 100 pharmaceutical companies in the United States and throughout the world. Over the past year, Dr. Preskorn has received grants/research support from or has served as a consultant, on the advisory board, or on the speakers bureau for the following: Abbott, Biovail, Boehringer-Ingelheim, Bristol-Myers Squibb, Cyberonics, Dey Pharma, Eisai, Johnson & Johnson, Lundbeck, Merck, National Institute of Mental Health, Naurex, Orexigen, Pierre Fabre, Pfizer, Stanley Medical Research Institute, Sunovion, and the U.S. Food and Drug Administration.