Permeability of Gemcitabine and PBPK Modeling to Assess Oral Administration

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Ferreira, A (Author) Other; Lapa, RAS (Author) FFUP; Nuno Vale (Author) FMUP

Journal

Title: Current Issues in Molecular Biology

Vol. 43

Pages: 2189-2198

ISSN: 1467-3037

Indexing

ISI Web of Knowledge - 0 Citations

Other information

Authenticus ID: P-00V-SZN

DOI: 10.3390/cimb43030153

Abstract (EN): Gemcitabine is a nucleoside analog effective against several solid tumors. Standard treatment consists of an intravenous infusion over 30 min. This is an invasive, uncomfortable and often painful method, involving recurring visits to the hospital and costs associated with medical staff and equipment. Gemcitabine's activity is significantly limited by numerous factors, including metabolic inactivation, rapid systemic clearance of gemcitabine and transporter deficiency-associated resistance. As such, there have been research efforts to improve gemcitabine-based therapy efficacy, as well as strategies to enhance its oral bioavailability. In this work, gemcitabine in vitro and clinical data were analyzed and in silico tools were used to study the pharmacokinetics of gemcitabine after oral administration following different regimens. Several physiologically based pharmacokinetic (PBPK) models were developed using simulation software GastroPlus (TM), predicting the PK parameters and plasma concentration-time profiles. The integrative biomedical data analyses presented here are promising, with some regimens of oral administration reaching higher AUC in comparison to the traditional IV infusion, supporting this route of administration as a viable alternative to IV infusions. This study further contributes to personalized health care based on potential new formulations for oral administration of gemcitabine, as well nanotechnology-based drug delivery systems.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10