Subhani Saima, Lukacova Viera, Kim Chaejin, Rodriguez-Vera Leyanis, Muniz Paula, Rodriguez Monica, Cristofoletti Rodrigo, Van Os Sandra, Suarez Elena, Schmidt Stephan, Vozmediano Valvanera
Center for Pharmacometrics and System Pharmacology at Lake Nona (Orlando), Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA.
Simulations Plus, Lancaster, CA 93534, USA.
Pharmaceutics. 2023 Feb 13;15(2):629. doi: 10.3390/pharmaceutics15020629.
Paliperidone was approved by the US FDA in 2006 as an extended-release (ER) tablet (Invega) for the once-daily treatment of schizophrenia. This osmotic-controlled release oral delivery system (OROS) offers advantages, such as the prevention of plasma concentration fluctuation and reduced dosing frequency. The administration of the ER after a high-fat/high-calorie meal leads to increased maximum plasma concentration and area under the curve values by 60% and 54%, respectively. Food has various effects on gastrointestinal (GI) physiology, including changed transit times, changed volumes, altered pH in different GI compartments, secretion of bile salts, and increased hepatic blood flow. This may affect solubility, the dissolution rate, absorption, and the pharmacokinetics. The aim of this study was to apply physiologically based absorption modeling (PBAM) to provide insights on paliperidone ER absorption under fed and fasting conditions. The PBAM adequately predicted absorption from the OROS formulation under both conditions. Absorption primarily occurs in the ascending colon and caecum. After a high-fat/high-calorie meal, absorption is increased through the jejunum, ileum, and colon due to either increased solubilization or the better efficiency of the OROS technology. PBAM-guided approaches can improve the understanding of branded drugs and thereby aid in guiding the development of generic formulations or formulation alternatives.
帕利哌酮于2006年被美国食品药品监督管理局批准为缓释（ER）片剂（Invega），用于精神分裂症的每日一次治疗。这种渗透控释口服给药系统（OROS）具有诸多优势，比如可防止血浆浓度波动并降低给药频率。高脂/高热量餐后服用ER会使最大血浆浓度和曲线下面积值分别增加60%和54%。食物对胃肠道（GI）生理有多种影响，包括改变转运时间、改变容积、改变不同胃肠道腔室的pH值、胆汁盐分泌以及增加肝血流量。这可能会影响溶解度、溶解速率、吸收以及药代动力学。本研究的目的是应用基于生理学的吸收建模（PBAM），以深入了解进食和空腹条件下帕利哌酮ER的吸收情况。PBAM在两种条件下均能充分预测OROS制剂的吸收情况。吸收主要发生在升结肠和盲肠。高脂/高热量餐后，由于增溶作用增强或OROS技术效率提高，空肠、回肠和结肠的吸收会增加。PBAM指导的方法可增进对品牌药物的理解，从而有助于指导仿制药或替代制剂的研发。
