title: Effect of carbamazepine on the pharmacokinetics of paliperidone extended-release tablets at steady-state.
abstract: Given the potential concomitant use of carbamazepine and paliperidone extended-release (ER) in the treatment of schizophrenia or schizoaffective disorder, this open-label, two-treatment sequential study investigated the effect of repeated administration of carbamazepine on the steady-state pharmacokinetics of paliperidone. Sixty-four patients with a diagnosis of schizophrenia or bipolar-I disorder received the following treatments in a fixed sequential order, without washout between treatments: (i) paliperidone ER 6 mg tablet once daily for 7 days, and (ii) paliperidone ER 6 mg once daily concomitantly with carbamazepine 200 mg twice daily for the subsequent 21 days. Upon coadministration with carbamazepine, paliperidone steady-state total exposure (AUC24 h ) and peak plasma concentrations (Cmax ) decreased by approximately 37% [LSM ratio-AUC24 h : 63.4 (90% CI: 57.19; 70.29); Cmax : 62.47 (90% CI: 55.77; 69.98)]. This decrease is accounted for to a substantial degree by a 35% increase in renal clearance of paliperidone, likely as a result of induction of renal P-glycoprotein by carbamazepine. A 14% decrease in the amount of drug excreted unchanged in the urine suggests that carbamazepine coadministration has a limited effect on the intestinal absorption or cytochrome metabolism of paliperidone.
authors.affiliation: Janssen Research and Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Virginie
authors.initials: V
authors.lastname: Kerbusch-Herben
authors.affiliation: Janssen Research and Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Adriaan
authors.initials: A
authors.lastname: Cleton
authors.affiliation: Janssen Research and Development, LLC, Raritan, NJ, USA.
authors.forename: Joris
authors.initials: J
authors.lastname: Berwaerts
authors.affiliation: Janssen Research and Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Vandebosch
authors.affiliation: Janssen Research and Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Remmerie
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D000328:Adult; D018692:Antimanic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001714:Bipolar Disorder / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000523:psychology; D002031:Bulgaria; D002220:Carbamazepine / Q000008:administration & dosage* / Q000009:adverse effects; D017523:Croatia; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D004339:Drug Compounding; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D000068882:Paliperidone Palmitate / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D065667:Renal Elimination / Q000187:drug effects; D012559:Schizophrenia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D018692:Antimanic Agents; D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D002220:Carbamazepine; D000068882:Paliperidone Palmitate
keywords: P-glycoprotein; antipsychotics; carbamazepine; drug interaction; paliperidone