Asbtract

Nintedanib (Nint), a tyrosine kinase inhibitor, is approved by the FDA for the treatment of idiopathic pulmonary fibrosis (IPF) by administration as an oral tablet. However, the oral bioavailability of Nint is extremely poor (<5%) due to minimal gastrointestinal absorption, P-gp-mediated efflux, which reduces drug uptake, and extensive first-pass hepatic metabolism. Along with high fecal excretion (93.4%), oral Nint also shows different adverse effects like nausea, vomiting, abdominal pain, and diarrhea, primarily due to the high dose requirement to achieve optimal therapeutic efficacy. To address these limitations, localized, non-invasive delivery of Nint by inhalation has been extensively investigated. Inhaled delivery can be achieved by either liquid (nebulized, metered dose inhaler) or as a solid (dry powder inhalation (DPI) drug product. Although many published studies on inhaled nintedanib highlight superior in vitro and preclinical data, few studies explore the clinical translation of inhaled Nint drug products. Here, we focus on developing a physiologically based pharmacokinetic (PBPK) model to predict the systemic and regional pharmacokinetic (PK) parameters of inhaled Nint when administered for a DPI drug product, using GastroPlus 9.9.

By Zia Uddin Masum & Vivek Gupta