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Journal of Psychiatric Practice:
doi: 10.1097/
COLUMNS: Psychopharmacology

Clinically Important Differences in the Pharmacokinetics of the Ten Newer “Atypical” Antipsychotics: Part 2. Metabolism and Elimination


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The “atypical” antipsychotics are grouped together based on what they are not (i.e., not dopamine-2 selective antagonists like haloperidol). While shar- ing this characteristic, these agents differ substan- tially in pharmacokinetics and pharmacodynamics. The first column in this series reviewed the bioavail- ability and half-life of the 10 newer “atypical” antipsychotics, including the most recently market- ed members of this class (asenapine, iloperidone, and lurasidone). This second column in the series discusses the metabolism of these agents, including principal enzyme(s) mediating each drug’s clear- ance and effects of co-administering substantial CYP enzyme inhibitors. Pharmacokinetic differ- ences among “atypical” antipsychotics can explain why some individuals may not respond to the usu- ally effective dose of a drug, while others may be especially sensitive to its dose-dependent adverse effects. For deeper understanding of the principles behind the specifics discussed here, the concepts of “special populations” and phase I versus phase II metabolism are discussed in the introduction. An understanding of these principals and the specific pharmacokinetic differences among the “atypical” antipsychotics can help clinicians optimize drug selection and dose for specific patients under spe- cific treatment conditions. The third column in this series will discuss the effects of hepatic and renal impairment on dosing recommendations, and a sub- sequent column in the series will review the sub- stantial and clinically important pharmacodynamic differences among these agents. (Journal of Psychiatric Practice 2012;18:361–368)

© 2012 Lippincott Williams & Wilkins, Inc.


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