biostudies-literatureGruber AF. Hoffmann-La Roche763-771https://www.ebi.ac.uk/biostudies/studies/S-EPMC5854746biostudies-literatureUnknown81(4)PURPOSE:In this study, a therapeutic drug monitoring (TDM) of erlotinib in pancreatic cancer patients was performed over 50 weeks to reveal possible alterations in erlotinib plasma concentrations. Additionally, a physiologically based pharmacokinetic (PBPK) model was created to assess such variations in silico. METHODS:Patients with advanced pancreatic cancer received a chemotherapeutic combination of 100 mg erlotinib q.d., 500-900 mg capecitabine b.d. and 5 mg/kg bevacizumab q.2wks. Samples were analyzed by HPLC and the results were compared to a PBPK model, built with the software GastroPlus™ and based on calculated and literature data. RESULTS:The erlotinib plasma concentrations did not show any accumulation, but displayed a high inter-patient variability over the whole investigated perCancer chemotherapy and pharmacologyMonitoring of erlotinib in pancreatic cancer patients during long-time administration and comparison to a physiologically based pharmacokinetic model.PMC5854746FA555004Gruber AKirchbaumer Baroian NSahmanovic Hrgovcic ACzejka MDittrich CKitzmueller MBuchner PfalseMonitoring of erlotinib in pancreatic cancer patients during long-time administration and comparison to a physiologically based pharmacokinetic model.PURPOSE:In this study, a therapeutic drug monitoring (TDM) of erlotinib in pancreatic cancer patients was performed over 50 weeks to reveal possible alterations in erlotinib plasma concentrations. Additionally, a physiologically based pharmacokinetic (PBPK) model was created to assess such variations in silico. METHODS:Patients with advanced pancreatic cancer received a chemotherapeutic combination of 100 mg erlotinib q.d., 500-900 mg capecitabine b.d. and 5 mg/kg bevacizumab q.2wks. Samples were analyzed by HPLC and the results were compared to a PBPK model, built with the software GastroPlus™ and based on calculated and literature data. RESULTS:The erlotinib plasma concentrations did not show any accumulation, but displayed a high inter-patient variability over the whole investigated per2018-01-01T00:00:00Z2018 Apr2025-04-18T11:49:54.117Z2019-06-06T19:08:35ZS-EPMC58547462945363510.1007/s00280-018-3545-4