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Current Drug Metabolism 2010-Jul

Atypical antipsychotic metabolism and excretion.

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J J Sheehan
J K Sliwa
J C Amatniek
A Grinspan
C M Canuso

Mo kle

Abstrè

BACKGROUND

The metabolic/biotransformation pathways of atypical antipsychotics (aripiprazole, clozapine, iloperidone, olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone) have been characterized and reviewed. However, comparisons of excretory pathways remain unexplored.

OBJECTIVE

To analyze the excretion profile of atypical antipsychotic agents and compare the overall magnitude of metabolism (changed vs. unchanged drug) and route of excretion (feces vs. urine). Secondary objectives include providing: 1) dosing information in hepatic and renal impairment, and 2) context of the specific enzymes and pathways involved in each agents' biotransformation.

METHODS

Published literature and each manufacturer's radiolabeled drug absorption, distribution, metabolism and excretion data and U.S. prescribing information were reviewed.

RESULTS

With the exception of paliperidone, atypical antipsychotics undergo extensive metabolism (i.e.,

CONCLUSIONS

Understanding the differences in the elimination profiles of atypical antipsychotics agents may permit better-informed drug and dose selection in special populations such as those with comorbid conditions (e.g. hepatitis, diabetes, end-stage renal disease) or pharmacogenetic variability; or at risk for drug-drug interactions. The use of patient tailored drug and dose-selection may result in greater treatment efficacy and a reduction in adverse events.

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