Case studies with mrgsolve: PBPK and QSP model implementation and utilization in R

Where / when

• University at Buffalo
  • 2018 CDSE Days (Buffalo, NY)
  • Tuesday, 10 April 9:30 am to 12:30 pm
• University of Florida
  • College of Pharmacy (Orlando Lake Nona Campus)
  • Saturday, 24 March 1:30 pm to 5:30 pm

Case Studies

Please see the reading list below for references for the case studies

QSP Models

• ERK inhibition in BRAF(V600E) mutant colorectal cancer
• OpenBoneMin: Bone marker and BMD changes under denosumab therapy

PBPK Models

• PBPK model for rifampicin / midazolam DDI
• Parameter optimization in PBPK model for statin/CsA DDI

Methods

• Global sensitivity analysis

Reading List

• Quantitative Analyses of Hepatic OATP-Mediated Interactions Between Statins and Inhibitors Using PBPK Modeling With a Parameter Optimization Method
  • Yoshikado T, Yoshida K, Kotani N, Nakada T, Asaumi R, Toshimoto K, Maeda K, Kusuhara H, Sugiyama Y. Clin Pharmacol Ther. 2016 Nov;100(5):513-523. PMID: 27170342
  • https://www.ncbi.nlm.nih.gov/pubmed/27170342
• Comprehensive PBPK Model of Rifampicin for Quantitative Prediction of Complex Drug-Drug Interactions: CYP3A/2C9 Induction and OATP Inhibition Effects
  • Asaumi R, Toshimoto K, Tobe Y, Hashizume K, Nunoya KI, Imawaka H, Lee W, Sugiyama Y. CPT Pharmacometrics Syst Pharmacol. 2018 Jan 25. PMID: 29368402
  • https://www.ncbi.nlm.nih.gov/pubmed/29368402
• Clinical responses to ERK inhibition in BRAF(V600E)-mutant colorectal cancer predicted using a computational model
  • Kirouac DC, Schaefer G, Chan J, Merchant M, Orr C, Huang SA, Moffat J, Liu L, Gadkar K, Ramanujan S. NPJ Syst Biol Appl. 2017 Jun 2;3:14. PubMed PMID: 28649441
  • https://www.ncbi.nlm.nih.gov/pubmed/28649441
• Predicting nonlinear changes in bone mineral density over time using a multiscale systems pharmacology model
  • Peterson MC, Riggs MM. CPT Pharmacometrics Syst Pharmacol. 2012 Nov 14;1:e14. PMID: 23835796
  • https://www.ncbi.nlm.nih.gov/pubmed/23835796
• Sobol Sensitivity Analysis: A Tool to Guide the Development and Evaluation of Systems Pharmacology Models
  • Zhang XY, Trame MN, Lesko LJ, Schmidt S. . CPT Pharmacometrics Syst Pharmacol. 2015 Feb;4(2):69-79. PMID: 27548289
  • https://www.ncbi.nlm.nih.gov/pubmed/27548289