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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The pharmacokinetics of paliperidone versus risperidone.

BACKGROUND: Several new atypical antipsychotics have become available for use, but knowledge about their pharmacology may not be widespread. OBJECTIVE: This review aims to increase awareness and knowledge about risperidone (R) and paliperidone (9-hydroxyrisperidone [9-OHR]), their pharmacokinetics, and pharmacodynamics. METHOD: The authors present a review of the literature on R and 9-OHR. RESULTS: Oral R may be approximately twice as potent as oral 9-OHR. Levels of R and 9-OHR in R-treated patients may help clinicians prescribe 9-OHR. In R-treated patients, the R/9-OHR concentration ratio is an index of CYP2D6 activity; an inverted ratio (>1) indicates a CYP2D6 poor metabolizer (PM) or the presence of a powerful CYP2D6 inhibitor. The concentration-to-dose (C/D) ratio, where C includes R+9-OHR, is an index of total clearance from the body. A C/D ratio decreased by half is associated with CYP3A inducers or a lack of compliance, whereas an increased C/D ratio may indicate CYP2D6 PM phenotype, use of CYP2D6 and/or CYP3A4 inhibitors, or, possibly, renal insufficiency. In in-vitro studies, R and 9-OHR have similar receptor binding (except for blocking alpha(1)). 9-OHR may have less ability to enter the brain because of greater affinity for the transporter P-glycoprotein. The limited available paliperidone pharmacokinetic information suggests that there are four minor metabolic pathways. In contrast to R treatment, being a CYP2D6 PM may not be clinically relevant for paliperidone treatment. Information on paliperidone drug-drug interactions is limited. Renal excretion may be the major route of paliperidone elimination. CONCLUSION: Clinicians can use R/9-OHR and the C/D ratios to interpret plasma R levels and guide treatment.[1]


  1. The pharmacokinetics of paliperidone versus risperidone. de Leon, J., Wynn, G., Sandson, N.B. Psychosomatics (2010) [Pubmed]
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