Development of a Physiologically Based Pharmacokinetic (PBPK) Model for Predicting Deposition and Disposition follo · g Inhaled and Intranasal Administration

Software: GastroPlus®
Division: Simulations Plus

Introduction & Background

The selection of a biologically active molecule as a successful inhaled therapeutic agent depends on its pharmacokinetic and safety properties and concentration profile(s) in both the plasma and the pulmonary tissues. In recent decades, pharmacokinetic (PK) modeling, especially Physiologically Based Pharmacokinetic (PBPK) modeling (1 ), has become a powerful tool for predicting concentration-time profiles for drugs of interest (2, 3). Extension of the PBPK methodology from traditional dosage forms to intranasal/inhalation routes could provide useful information for the design and selection of drug candidates.  This work describes the extension of the modeling and simulation software GastroPlusTM (Simulations Plus, Inc.) (4), to include administration via inhaled and intranasal routes and its application to mechanistically model disposition following pulmonary administration of budesonide, a non­halogenated corticosteroid that is among the most effective inhaled medications available for patients with persistent asthma (5).

By Neil A. Miller, Siladitya Ray Chadhuri, Viera Lukacova, Valeriu Damian-Lordache, Martin K. Bayliss and Walter S Woltosz

Respiratory Drug Delivery January 1, 2010