Clinically important differences in the pharmacokinetics of the ten newer "atypical" antipsychotics: part 1

The "atypical" antipsychotics are grouped together by what they are not (i.e., not dopamine-2 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.