Leveraging Physiologically Based Modelling to Provide Insights on the Absorption of Paliperidone Extended-Release Formulation under Fed and Fasting Conditions
Saima Subhani,
Viera Lukacova,
Chaejin Kim,
Leyanis Rodriguez-Vera,
Paula Muniz,
Monica Rodriguez,
Rodrigo Cristofoletti,
Sandra Van Os,
Elena Suarez,
Stephan Schmidt,
Valvanera Vozmediano
Affiliations
Saima Subhani
Center for Pharmacometrics and System Pharmacology at Lake Nona (Orlando), Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA
Viera Lukacova
Simulations Plus, Lancaster, CA 93534, USA
Chaejin Kim
Center for Pharmacometrics and System Pharmacology at Lake Nona (Orlando), Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA
Leyanis Rodriguez-Vera
Center for Pharmacometrics and System Pharmacology at Lake Nona (Orlando), Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA
Paula Muniz
Model Informed Development, CTI Laboratories Spain, Derio, 48160 Bizkaia, Spain
Monica Rodriguez
Model Informed Development, CTI Laboratories Spain, Derio, 48160 Bizkaia, Spain
Rodrigo Cristofoletti
Center for Pharmacometrics and System Pharmacology at Lake Nona (Orlando), Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA
Sandra Van Os
Synthon BV, 6545 CM Nijmegen, The Netherlands
Elena Suarez
Pharmacokinetic, Nanotechnology and Gene Therapy Group (PharmaNanoGene), Department of Pharmacology, School of Medicine and Nursing, University of the Basque Country UPV/EHU, 48940 Bizkaia, Spain
Stephan Schmidt
Center for Pharmacometrics and System Pharmacology at Lake Nona (Orlando), Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA
Valvanera Vozmediano
Center for Pharmacometrics and System Pharmacology at Lake Nona (Orlando), Department of Pharmaceutics, College of Pharmacy, University of Florida, Orlando, FL 32827, USA
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.
