title: Single- and multiple-dose pharmacokinetics and dose proportionality of the psychotropic agent paliperidone extended release.
abstract: Paliperidone extended-release tablet (paliperidone ER) is a centrally active dopamine D(2)- and serotonergic 5-HT(2A)-receptor antagonist that is registered for the treatment of schizophrenia. The controlled rate of release of paliperidone from the ER formulation is designed to have a slower absorption rate, which results in gradual ascending plasma concentrations with observed maximum plasma concentrations occurring at 24 hours after dosing on the first dosing day. On subsequent treatment days, the ER formulation provides minimal fluctuations in plasma concentrations. Paliperidone is eliminated with a terminal half-life of approximately 24 hours. Steady state is achieved after 4 daily doses. Paliperidone ER exhibits time-invariant pharmacokinetics. It shows a 3.5-fold accumulation upon steady state, mainly caused by the controlled release characteristics of the formulation. Paliperidone ER displays dose proportionality over the dose range of 3 to 15 mg; the 90% confidence intervals of the pairwise dose comparisons are all included in the 80% to 125% bioequivalence limits.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, a division of Janssen Pharmaceutica NV, B-2340 Beerse, Belgium. nvossela@its.jnj.com
authors.forename: Sandra
authors.initials: S
authors.lastname: Boom
authors.forename: Krishna
authors.initials: K
authors.lastname: Talluri
authors.forename: Luc
authors.initials: L
authors.lastname: Janssens
authors.forename: Bart
authors.initials: B
authors.lastname: Remmerie
authors.forename: Marc
authors.initials: M
authors.lastname: De Meulder
authors.forename: Stefaan
authors.initials: S
authors.lastname: Rossenu
authors.forename: Nancy
authors.initials: N
authors.lastname: van Osselaer
authors.forename: Marielle
authors.initials: M
authors.lastname: Eerdekens
authors.forename: Adriaan
authors.initials: A
authors.lastname: Cleton
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D000068882:Paliperidone Palmitate; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D011897:Random Allocation
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D007555:Isoxazoles; D011743:Pyrimidines; D000068882:Paliperidone Palmitate