Clinically important differences in the pharmacokinetics of the ten newer "atypical" antipsychotics: Part 2. Metabolism and elimination.

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 column in this series reviewed the bioavailability 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 clearance and effects of co-administering substantial CYP enzyme inhibitors. 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. 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 specific treatment conditions. The third column in this series will discuss the effects of hepatic and renal impairment on dosing recommendations, and a subsequent column in the series will review the substantial and clinically important pharmacodynamic differences among these agents.