The Pharmacokinetics of Paliperidone Versus Risperidone

Abstract

Several new atypical antipsychotics have become available for use, but knowledge about their pharmacology may not be widespread. This review aims to increase awareness and knowledge about risperidone (R) and paliperidone (9-hydroxyrisperidone [9-OHR]), their pharmacokinetics, and pharmacodynamics. The authors present a review of the literature on R and 9-OHR. 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. Clinicians can use R/9-OHR and the C/D ratios to interpret plasma R levels and guide treatment.