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PII‐72
Author(s) -
Cleton A.,
Rossenu S.,
Vermeulen A.,
Cleton A.,
Talluri K.,
Mertens A.,
Janssens L.,
Boom S.
Publication year - 2006
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2005.12.197
Subject(s) - paliperidone , enantiomer , pharmacokinetics , pharmacology , medicine , chemistry , stereochemistry , schizophrenia (object oriented programming) , psychiatry , antipsychotic
BACKGROUND/AIMS Paliperidone is a mixture of two equally potent enantiomers. The proposed pharmacokinetic model aims at characterizing the pharmacokinetics of the two enantiomers of Paliperidone and their interconversion. METHODS In this single‐dose, 5‐period cross over study, 20 subjects were randomised to receive either a 30 min i.v. infusion of 1 mg Paliperidone, a 1 mg Immediate Release (IR) formulation or an 1 mg solution of the (+) or (−) enantiomer, a 3 mg Extended Release (ER) formulation of Paliperidone. RESULTS Plasma concentration‐time profiles of each enantiomer were best described by a 2 compartment pharmacokinetic model, with a lag time after oral administration. The median volume of the peripheral compartment is much higher for the (−) enantiomer (192 L) compared to the (+) enantiomer (70.6 L). The intercompartment clearance of the (+) enantiomer is lower than for the (−) enantiomer, 78.8 L/h and 282 L/h. The elimination clearance of the (+) enantiomer is lower than the clearance of the (−) enantiomer, 1.41 and 8.15 L/h. The interconversion clearance (CLi) between both enantiomers is 7.90 L/h and independent of (+) to (−) or (−) to (+) interconversion. The bioavailability after administration of the IR was 121% and for ER formulation 28%. CONCLUSION With this study a pharmacokinetic model has been developed to describe the disposition of Paliperidone and to characterise the interconversion between the two enantiomers of Paliperidone. Clinical Pharmacology & Therapeutics (2005) 79 , P55–P55; doi: 10.1016/j.clpt.2005.12.197