April - June 2010, Volume 6, Issue 2

Voicu V, Medvedovici A, Miron D, Radulescu F

A novel approach on pharmacokinetic/pharmacodynamic correlations of risperidone: understanding its safety and efficacy profiles

Acta Endo (Buc) 2010, 6 (2): 265-285
doi: 10.4183/aeb.2010.265

The pharmacokinetic characteristics of a compound as well as the immediate consequences of its physicochemical behavior during interactions with biological structures,\r\nrepresent the key issues for its pharmacodynamic profile, starting from the most fundamental global aspects (i.e. central and / or peripheral action) to the most detailed ones (i.e. molecular mechanism of action).\r\nSuccessive metabolic reactions lead to either bioactivation or bioinactivation of themolecular entity. A particular importance is currently assigned to several molecular\r\nphysicochemical descriptors, for instance the polarity degree (mirroring the changes of partition coefficients and of the permeability of biological structures), and emphasizing on distribution and renal excretion rate.\r\nThe active metabolite (9-hydroxy-risperidone) of the atypical antipsychotic agent risperidone has an increased polar character and, consequently, its pharmacokinetic profile is modified compared to the parent drug: especially the penetration through the bood brain barrier and the efflux pump mediated transport were considered. In this context, the kinetic characteristics and their correlation with the pharmacodynamic properties for the two active\r\nentities, as well as the consequences dealing with the antipsychotic efficacy, the safety and efficacy profiles can be anticipated. The present approach critically asseses the available data from literature corroborated with the personal findings over the last years.

Keywords: risperidone, 9-hydroxy-risperidone, pharmacokinetic / pharmacodynamic correlations

Correspondence: Prof. V. A. Voicu, MD, Member of the Romanian Academy, ?Carol Davila? University of Medicine and Pharmacy Bucharest, 70th Ion Neculce street, Bucharest-011256, Romania, fax +40213112993, e-mail victor.voicu@yahoo.com