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Clinically Important Differences in the Pharmacokinetics of the Ten Newer “Atypical” Antipsychotics

Part 1


Journal of Psychiatric Practice®: May 2012 - Volume 18 - Issue 3 - p 199–204
doi: 10.1097/01.pra.0000415076.28497.8e
COLUMNS: Psychopharmacology

The “atypical” antipsychotics are grouped together by what they are not (i.e., not dopamine2 selective antagonists like haloperidol). While sharing that characteristic, these agents differ substantially in pharmacokinetics and pharmacodynamics. This column, the first in a series on these agents, reviews the bioavailability and half-life of the 10 newer “atypical” antipsychotics, including the most recently marketed members of this class (asenapine, iloperidone, and lurasidone). Drugs with high oral bioavailability are generally less susceptible to diet or drug-drug interactions affecting first pass metabolism. The converse is true for drugs with lower oral bioavailability (e.g., they may have a food effect in which oral bioavailability is decreased in the fasted versus fed state). The half-life of an antipsychotic agent in large measure determines whether it can be safely and effectively administered once a day, at least in an immediate release formulation. Pharmacokinetic differences among atypical antipsychotics can explain why some individuals may not respond to the usually effective dose of a drug, while others may be especially sensitive to its dose-dependent adverse effects. An understanding of pharmacokinetic differences among the atypical antipsychotics can help clinicians optimize drug selection and dose for specific patients under specific treatment conditions. Subsequent columns in this series on atypical antipsychotics will discuss their metabolism, including the principal enzyme(s) mediating each drug’s clearance, effects of co-administration of substantial CYP enzyme inhibitors, effect of hepatic and renal impairment, and the substantial and clinically important pharmacodynamic differences among these agents. (Journal of Psychiatric Practice 2012;18:199–204)

SHELDON H. PRESKORN, MD, is Professor, Department of Psychiatry, University of Kansas School of Medicine-Wichita, and Chief Science Officer and Medical Direc tor, 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 300 clinical trials including every antidepressant marketed in the United States over a period of 25 years. Dr. Preskorn maintains a website at where readers can access previous columns and other publications.

Disclosure statement: During a career of over 30 years in clinical psychopharmacology, Dr. Preskorn has worked with over 85 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 for, 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. Of special relevance to this series, Dr. Preskorn has over his career been an investigator on either industry and/or federally sponsored studies of every antipsychotic mentioned in this series.

Copyright © 2012 Wolters Kluwer Health, Inc. All rights reserved.