The pharmacokinetics of paliperidone versus risperidone

Jose De Leon, Gary Wynn, Neil B. Sandson

Research output: Contribution to journalReview articlepeer-review

107 Scopus citations


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 invitro studies, R and 9-OHR have similar receptor binding (except for blocking α1). 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.

Original languageEnglish
Pages (from-to)80-88
Number of pages9
Issue number1
StatePublished - 2010

Bibliographical note

Funding Information:
Dr. de Leon is the Medical Director of the University of Kentucky Mental Health Research Center, Eastern State Hospital, Lexington; Professor of Psychiatry, College of Medicine, University of Kentucky, Lexington, and Visiting Professor at the Dept. of Psychiatry and Institute of Neurosciences, University of Granada, Granada, Spain. Dr. de Leon is currently a co-investigator in an NIH Small Business Innovation Research Grant awarded to Genomas, Inc. In the past 4 years (since October 1, 2005), Dr. de Leon has received two researcher-initiated grants, one from Roche Molecular Systems, Inc. , for this study, and one from Eli Lilly (the latter as co-investigator). He was on the advisory board of Roche Molecular Systems, Inc. (2006). He personally develops his presentations for lecturing and has never lectured using any pharmaceutical company presentations. In the last 4 years (since October 1, 2005) he has received lecture support from Roche Molecular Systems, Inc. (2006), Eli Lilly (2006), Janssen (2006), and Bristol-Myers Squibb (2006). He has never been a consultant and has no other financial arrangements with pharmacogenetic or pharmaceutical companies nor owns any of their stock.

ASJC Scopus subject areas

  • Arts and Humanities (miscellaneous)
  • Applied Psychology
  • Psychiatry and Mental health


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