Janssen Research and Development, Division of Janssen Pharmaceutica NV, Beerse, Belgium.
Janssen Research and Development, LLC, Raritan, NJ, USA.
Clin Pharmacol Drug Dev. 2014 Sep;3(5):371-7. doi: 10.1002/cpdd.122. Epub 2014 May 26.
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.
鉴于卡马西平与帕利哌酮缓释片（ER）可能同时用于治疗精神分裂症或分裂情感障碍，本开放性、两治疗顺序研究调查了卡马西平重复给药对帕利哌酮稳态药代动力学的影响。64 名精神分裂症或双相 I 障碍患者以固定顺序接受以下治疗，两种治疗之间无洗脱期：（i）帕利哌酮 ER 6mg 片剂每日一次，连用 7 天，和（ii）帕利哌酮 ER 6mg 每日一次，同时合用卡马西平 200mg 每日两次，随后 21 天。与卡马西平合用后，帕利哌酮稳态总暴露量（AUC24h）和峰血浆浓度（Cmax）降低约 37%[LSM 比值-AUC24h：63.4（90%CI：57.19；70.29）；Cmax：62.47（90%CI：55.77；69.98）]。这种降低在很大程度上归因于帕利哌酮肾清除率增加 35%，可能是由于卡马西平诱导了肾 P-糖蛋白。尿液中未变化的药物排泄量减少 14%，表明卡马西平合用对帕利哌酮的肠道吸收或细胞色素代谢仅有有限影响。
