Pharmacokinetics of Anti-VEGF Agent aflibercept in cancer predicted by data-driven, molecular-detailed model

CPT: Pharmacometrics and Systems Pharmacology

Volumn 4, Issue 11, 2015, Pages 641-649

  Finley, S D ^a   Angelikopoulos, P ^b   Koumoutsakos, P ^b   Popel, A S ^c  

^a University of Southern California ^*  (United States)

^b ETH ZURICH   (Switzerland)

^c JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AFLIBERCEPT; VASCULOTROPIN;

ANTIANGIOGENIC ACTIVITY; ARTICLE; BAYES THEOREM; COMPUTER MODEL; COMPUTER SIMULATION; DRUG DEGRADATION; INTERNALIZATION; MOLECULAR INTERACTION; PHARMACOKINETICS; PRIORITY JOURNAL; PROTEIN DEGRADATION; STEADY STATE;

EID: 84956584796     PISSN: None     EISSN: 21638306     Source Type: Journal    
DOI: 10.1002/psp4.12040     Document Type: Article

References (24)

1. Rudge J.S., et al. VEGF Trap complex formation measures production rates of VEGF, providing a biomarker for predicting efficacious angiogenic blockade. Proc. Natl. Acad. Sci. USA 104, 18363-18370 (2007
2. Zhou Q., & Gallo J.M. The pharmacokinetic/pharmacodynamic pipeline: translating anticancer drug pharmacology to the clinic. AAPS J. 13, 111-120 (2011
3. Gallo J.M. Pharmacokinetic/pharmacodynamic-driven drug development. Mt. Sinai J. Med. 77, 381-388 (2010
4. Mager D.E., & Jusko W.J. Development of translational pharmacokineticpharmacodynamic models. Clin. Pharmacol. Ther. 83, 909-912 (2008
5. Kuepfer L., Lippert J., & Eissing T. Multiscale mechanistic modeling in pharmaceutical research and development. In: Advances in Systems Biology (eds. Goryanin I.I., & Goryachev A.B.) 543-561 (Springer New York, New York, 2012
6. Rowland M., Peck C., & Tucker G. Physiologically-based pharmacokinetics in drug development and regulatory science. Annu. Rev. Pharmacol. Toxicol. 51, 45-73 (2011
7. Sharan S., & Woo S. Systems pharmacology approaches for optimization of antiangiogenic therapies: challenges and opportunities. Front. Pharmacol. 6, 33 (2015
8. Finley S.D., Chu L.H., & Popel A.S. Computational systems biology approaches to anti-angiogenic cancer therapeutics. Drug Discov. Today 20, 187-197 (2015
9. Thai H.T., Veyrat-Follet C., Mentr-e, F., & Comets E. Population pharmacokinetic analysis of free and bound aflibercept in patients with advanced solid tumors. Cancer Chemother. Pharmacol. 72, 167-180 (2013
10. Thai H.T., Mentr-e, F., Holford N.H., Veyrat-Follet C., & Comets E. Evaluation of bootstrap methods for estimating uncertainty of parameters in nonlinear mixed-effects models: a simulation study in population pharmacokinetics. J. Pharmacokinet. Pharmacodyn. 41, 15-33 (2014
11. Panoilia E., et al. A pharmacokinetic binding model for bevacizumab and VEGF165 in colorectal cancer patients. Cancer Chemother. Pharmacol. 75, 791-803 (2015
12. Stefanini M.O., Wu F.T., Mac Gabhann F., & Popel A.S. A compartment model of VEGF distribution in blood, healthy and diseased tissues. BMC Syst. Biol. 2, 77 (2008
13. Finley S.D., Engel-Stefanini M.O., Imoukhuede P.I., & Popel A.S. Pharmacokinetics and pharmacodynamics of VEGF-neutralizing antibodies. BMC Syst. Biol. 5, 193 (2011
14. Finley S.D., & Popel A.S. Predicting the effects of anti-angiogenic agents targeting specific VEGF isoforms. AAPS J. 14, 500-509 (2012
15. Finley S.D., & Popel A.S. Effect of tumor microenvironment on tumor VEGF during anti-VEGF treatment: systems biology predictions. J. Natl. Cancer Inst. 105, 802-811 (2013
16. Angelikopoulos P., Papadimitriou C., & Koumoutsakos P. Bayesian uncertainty quantification and propagation in molecular dynamics simulations: a high performance computing framework. J. Chem. Phys. 137, 144103 (2012
17. Hadjidoukas P.E., Angelikopoulos P., Rossinelli D., Alexeev D., Papadimitriou C., & Koumoutsakos P. Bayesian uncertainty quantification and propagation for discrete element simulations of granular materials. Comput. Methods Appl. Mech. Eng. 282, 218-238 (2014
18. Hadjidoukas P.E., Angelikopoulos P., Papadimitriou C., & Koumoutsakos P. P4U: A high performance computing framework for Bayesian uncertainty quantification of complex models. J. Comput. Phys. 284, 1-21 (2015
19. Imoukhuede P.I., & Popel A.S. Quantification and cell-to-cell variation of vascular endothelial growth factor receptors. Exp. Cell Res. 317, 955-965 (2011
20. Imoukhuede P.I., & Popel A.S. Expression of VEGF receptors on endothelial cells in mouse skeletal muscle. PLoS One 7, e44791 (2012
21. Finley S.D., Dhar M., & Popel A.S. Compartment model predicts VEGF secretion and investigates the effects of VEGF trap in tumor-bearing mice. Front. Oncol. 3, 196 (2013
22. Stefanini M.O., Wu F.T., Mac Gabhann F., & Popel A.S. The presence of VEGF receptors on the luminal surface of endothelial cells affects VEGF distribution and VEGF signaling. PLoS Comput. Biol. 5, e1000622 (2009
23. Lockhart A.C., et al. Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. J. Clin. Oncol. 28, 207-214 (2010
24. Dixon J.A., Oliver S.C., Olson J.L., & Mandava N. VEGF Trap-Eye for the treatment of neovascular age-related macular degeneration. Expert Opin. Investig. Drugs 18, 1573-1580 (2009