Effect of carbamazepine on the pharmacokinetics of paliperidone extended-release tablets at steady-state. 2014

Virginie Kerbusch-Herben, and Adriaan Cleton, and Joris Berwaerts, and An Vandebosch, and Bart Remmerie
Janssen Research and Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium.

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.

UI MeSH Term Description Entries
D007408 Intestinal Absorption Uptake of substances through the lining of the INTESTINES. Absorption, Intestinal
D008297 Male Males
D008657 Metabolic Clearance Rate Volume of biological fluid completely cleared of drug metabolites as measured in unit time. Elimination occurs as a result of metabolic processes in the kidney, liver, saliva, sweat, intestine, heart, brain, or other site. Total Body Clearance Rate,Clearance Rate, Metabolic,Clearance Rates, Metabolic,Metabolic Clearance Rates,Rate, Metabolic Clearance,Rates, Metabolic Clearance
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D002031 Bulgaria A country in Southeastern Europe, bordering the Black Sea, between Romania and Turkey. The capital is Sofia.
D002220 Carbamazepine A dibenzazepine that acts as a sodium channel blocker. It is used as an anticonvulsant for the treatment of grand mal and psychomotor or focal SEIZURES. It may also be used in the management of BIPOLAR DISORDER, and has analgesic properties. Amizepine,Carbamazepine Acetate,Carbamazepine Anhydrous,Carbamazepine Dihydrate,Carbamazepine Hydrochloride,Carbamazepine L-Tartrate (4:1),Carbamazepine Phosphate,Carbamazepine Sulfate (2:1),Carbazepin,Epitol,Finlepsin,Neurotol,Tegretol
D003692 Delayed-Action Preparations Dosage forms of a drug that act over a period of time by controlled-release processes or technology. Controlled Release Formulation,Controlled-Release Formulation,Controlled-Release Preparation,Delayed-Action Preparation,Depot Preparation,Depot Preparations,Extended Release Formulation,Extended Release Preparation,Prolonged-Action Preparation,Prolonged-Action Preparations,Sustained Release Formulation,Sustained-Release Preparation,Sustained-Release Preparations,Timed-Release Preparation,Timed-Release Preparations,Controlled-Release Formulations,Controlled-Release Preparations,Extended Release Formulations,Extended Release Preparations,Slow Release Formulation,Sustained Release Formulations,Controlled Release Formulations,Controlled Release Preparation,Controlled Release Preparations,Delayed Action Preparation,Delayed Action Preparations,Formulation, Controlled Release,Formulations, Controlled Release,Prolonged Action Preparation,Release Formulation, Controlled,Release Formulations, Controlled,Sustained Release Preparation,Timed Release Preparation,Timed Release Preparations
D004334 Drug Administration Schedule Time schedule for administration of a drug in order to achieve optimum effectiveness and convenience. Administration Schedule, Drug,Administration Schedules, Drug,Drug Administration Schedules,Schedule, Drug Administration,Schedules, Drug Administration
D004339 Drug Compounding The preparation, mixing, and assembly of a drug. (From Remington, The Science and Practice of Pharmacy, 19th ed, p1814). Drug Formulation,Drug Preparation,Drug Microencapsulation,Pharmaceutical Formulation,Compounding, Drug,Formulation, Drug,Formulation, Pharmaceutical,Microencapsulation, Drug,Preparation, Drug
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug

Related Publications

Virginie Kerbusch-Herben, and Adriaan Cleton, and Joris Berwaerts, and An Vandebosch, and Bart Remmerie
July 2010, Human psychopharmacology,
Virginie Kerbusch-Herben, and Adriaan Cleton, and Joris Berwaerts, and An Vandebosch, and Bart Remmerie
August 1993, International journal of clinical pharmacology, therapy, and toxicology,
Virginie Kerbusch-Herben, and Adriaan Cleton, and Joris Berwaerts, and An Vandebosch, and Bart Remmerie
May 2007, Journal of psychosocial nursing and mental health services,
Virginie Kerbusch-Herben, and Adriaan Cleton, and Joris Berwaerts, and An Vandebosch, and Bart Remmerie
December 2006, Journal of the American Academy of Child and Adolescent Psychiatry,
Virginie Kerbusch-Herben, and Adriaan Cleton, and Joris Berwaerts, and An Vandebosch, and Bart Remmerie
January 1991, Pharmacotherapy,
Virginie Kerbusch-Herben, and Adriaan Cleton, and Joris Berwaerts, and An Vandebosch, and Bart Remmerie
January 2005, Clinical pharmacokinetics,
Virginie Kerbusch-Herben, and Adriaan Cleton, and Joris Berwaerts, and An Vandebosch, and Bart Remmerie
October 2005, Current medical research and opinion,
Virginie Kerbusch-Herben, and Adriaan Cleton, and Joris Berwaerts, and An Vandebosch, and Bart Remmerie
January 2000, British journal of clinical pharmacology,
Virginie Kerbusch-Herben, and Adriaan Cleton, and Joris Berwaerts, and An Vandebosch, and Bart Remmerie
March 1993, Epilepsy research,
Virginie Kerbusch-Herben, and Adriaan Cleton, and Joris Berwaerts, and An Vandebosch, and Bart Remmerie
April 1988, Antimicrobial agents and chemotherapy,
Copied contents to your clipboard!