Alumni Profiles

Chris Penland

  • Program Years: 1993-1997
  • Academic Institution: Duke University
  • Field of Study: Biomedical Engineering: Cardiac Electrophysiology
  • Academic Advisor: Craig Henrique
  • Practicum(s):
    Oak Ridge National Laboratory (1994)
  • Degree(s):
    Ph.D. Biomedical Engineering, Duke University, 2002
    M.S. Nuclear Engineering, North Carolina State University, 1995
    B.S. Nuclear Engineering, North Carolina State University, 1993

Current Status

  • Status: Sr Group Director, Clinical Pharmacology & Pharmacometrics - AstraZeneca Pharmaceuticals
  • Research Area: Computational and Statistical Modeling of Pharmacokinetic/Pharmacodynamic Systems for Biopharma

Publications

Cardiovascular and renal safety of metformin in patients with diabetes and moderate or severe chronic kidney disease: observations from the EXSCEL and SAVOR-TIMI 53 cardiovascular outcomes trials. Clegg LE, Jing Y, Penland RC, Boulton DW, Hernandez AF, Holman RR, Vora J. Diabetes Obes Metab. 2021 Jan 4. doi: 10.1111/dom.14313.
A model-based approach to investigate the relationship between glucose-insulin dynamics and dapagliflozin treatment effect in patients with T2DM. Shah M, Stolbov L, Yakovleva T, Tang W, Sokolov V, Penland RC, Boulton DW, Parkinson J. Diabetes Obes Metab. 2020 Dec 23. doi: 10.1111/dom.14305.
Renal Effects of Dapagliflozin in People with and without Diabetes with Moderate or Severe Renal Dysfunction: Prospective Modeling of an Ongoing Clinical Trial. Hallow KM, Boulton DW, Penland RC, Helmlinger G, Nieves EH, van Raalte DH, Heerspink HJL, Greasley PJ. J Pharmacol Exp Ther 2020 Oct;375(1):76-91. doi: 10.1124/jpet.120.000040.
Effect of once-weekly exenatide on estimated glomerular filtration rate slope depends on baseline renal risk: A post hoc analysis of the EXSCEL trial. van der Aart-van der Beek AM, Clegg LE, Penland RC, Boulton DW, Sjöström CD, Mentz RJ, Holman RR, Heerspink HJL. Diabetes Obes Metab. 2020 Dec;22(12):2493-2498. doi: 10.1111/dom.14175.
Predicted cardiac hemodynamic consequences of the renal actions of SGLT2i in the DAPA-HF study population: A mathematical modeling analysis. Yu H, Tang W, Greasley PJ, Penland RC, Boulton DW, Hallow KM. J Clin Pharmacol. 2020 Oct 22 doi: 10.1002/jcph.1769.
Quantitative systems pharmacology modeling of renal glucose reabsorption in type 2 diabetes: Differential inhibition of SGLT1 by canagliflozin vs. dapagliflozin and empagliflozin. Sokolov V, Yakovleva T, Chu L, Tang W, Greasley PJ, Johansson S, Peskov K, Helmlinger G, Boulton DW, Penland RC. CPT Pharmacometrics Syst Pharmacol, 9: 222-229, 2020. doi:10.1002/psp4.12498.
Effects of exenatide and open-label SGLT2 inhibitor treatment, given in parallel or sequentially, on mortality and cardiovascular and renal outcomes in type 2 diabetes: insights from the EXSCEL trial. Clegg LE, Penland RC, Bachina S, Boulton DW, Thuresson M, Heerspink HJL, Gustavson S, Sjostrom CD, Ruggles JA, Hernandez AF, Buse JB, Mentz RJ, Holman RR. Cardiovasc Diabetol 18:138, 2019.
Urinary glucose excretion contributions of SGLT2 vs. SGLT1 transporters: a quantitative systems pharmacology analysis in healthy and T2DM subjects administered SGLT2 inhibitors. T Yakovleva, V Sokolov, L Chu, W Tang, PJ Greasley, H Peilot Sjögren, S Johansson, K Peskov, G Helmlinger, DW Boulton, RC Penland. Diabetes Obes Metab 2019.
Glucosuria-Related Adverse Events for the SGLT2 Inhibitors Dapagliflozin and Canagliflozin: A Meta-Analysis. L Chu, T Yakovleva, V Sokolov, G Helmlinger, W Tang, S Johansson, S Aksenov, PJ Greasley, K Peskov, DW Boulton, RC Penland. Diabetes Obes Metab 2019, submitted.
Prediction and validation of exenatide risk marker effects on progression of renal disease: Insights from EXSCEL. NMA Idzerda, LE Clegg, AF Hernandez, G Bakris, RC Penland, DW Boulton, MA Bethel, RR Holman, HJL Heerspink. ASN Kidney Week, November 2019, Washington DC USA.
Prediction and validation of exenatide risk marker effects on progression of renal disease: Insights from EXSCEL. NMA Idzerda, LE Clegg, AF Hernandez, G Bakris, RC Penland, DW Boulton, MA Bethel, RR Holman, HJL Heerspink. Clin J Am Soc Nephrol 2019, submitted.
Quantitative systems pharmacology: An exemplar model building workflow with applications in cardiovascular, metabolic and oncology drug development. G Helmlinger, V Sokolov, K Peskov, KM Hallow, Y Kosinsky, V Voronova, L Chu, T Yakovleva, I Azarov, D Kaschek, A Dolgun, H Schmidt, DW Boulton, RC Penland. CPT: PSP 2019.
Urinary glucose excretion after dapagliflozin treatment: an exposure–response modeling comparison between Japanese and non-Japanese patients diagnosed with Type 1 Diabetes Mellitus. Sokolov V, Yakovleva T, Ueda S, Parkinson J, Boulton DW, Penland RC, Tang W. Diabetes Obes Metab 2019;21:829–836.
Reduction of cardiovascular risk and improved estimated glomerular filtration rate by SGLT2 inhibitors, including dapagliflozin, is consistent across the class: an analysis of the placebo arm of EXSCEL. Clegg LE, Heerspink HJL, Penland RC, Teng W, Boulton DW, Bachina S, Fox RD, Fenici P, Thuresson M, Mentz RJ, Hernandez AF, Holman RR. Diabetes Care 2018:1-5.
Exenatide effects on gastric emptying and oral glucose appearance in plasma: A quantitative assessment using an integrative systems pharmacology model. Voronova V, Zhudenkov K, Penland RC, Boulton DW, Helmlinger G, Peskov K. Diabetes Obes Metab 2018:20:2034–2038.
Dapaglifozin preserves renal function in patients with T2DM: a longitudinal meta-analysis of eGFR across clinical trials. Johansson S, Hamrén B, Åstrand M, Penland RC, Boulton DW. European Association for the Study of Diabetes 2018. Encore presented at WCIRDC 2018.
Dapagliflozin pharmacokinetics are similar in patients with type 1 and type 2 diabetes mellitus. Melin J, Parkinson J, Rekic D, Hamren B, Penland RC, Boulton DW, Tang W. Population Approach Group Europe (PAGE) 2018.
Drug-disease systems modeling to identify informative covariates necessary for precise prediction of renal glucose reabsorption and urinary glucose excretion with SGLT2 inhibitors. Yakovleva T, Sokolov V, Chu L, Penland RC, Tang W, Greasley PJ, Johansson S, Peskov K, Helmlinger G, Boulton DW. Population Approach Group Europe (PAGE) 2018.
Impact of SGLT2 inhibitors on reducing cardiovascular risk and improving estimated glomerular filtration rate in the EXSCEL placebo arm. Clegg L, Heerspink HJL, Penland RC, Tang W, Boulton DW, Bachina S, Fox RD, Fenici P, Thuresson M, Hernandez AF, Bethel MA, Holman RR. 78th Scientific Sessions of the American Diabetes Association, Orlando FL USA, June 2018.
Dapagliflozin exposure–response in Japanese versus non-Japanese patients with type 1 diabetes. Sokolov V, Yakovleva T, Ueda S, Parkinson J, Penland RC, Boulton DW, Tang W. 78th Scientific Sessions of the American Diabetes Association, Orlando FL USA, June 2018.
Drug‐disease modeling of renal glucose reabsorption in healthy and diabetes subjects: Investigating differences in SGLT2i efficacy. Yakovleva T, Sokolov V, Chu L, Penland RC, Tang W, Greasley PJ, Johansson S, Peskov K, Helmlinger G, Boulton DW. American Conference on Pharmacometrics (ACoP) Fort Lauderdale FL USA, October 2017.
Population pharmacokinetic and exposure–response models of once-weekly exenatide. Penland RC, Aksenov S, Någård M, Johansson S, Boulton DW, Cirincione B. American Conference on Pharmacometrics (ACoP) Fort Lauderdale FL USA, October 2017.
Simulated exenatide plasma concentrations in human subjects resulting from modifications to regular dosing of EQWS. Penland RC, Någård M, Johansson S, Boulton DW. American Conference on Pharmacometrics (ACoP) Fort Lauderdale FL USA, October 2017.
Model‐based meta‐analysis of glucosuria‐related adverse events in SGLT2 inhibitors. Chu L, Penland RC, Helmlinger G, Boulton DW. American Conference on Pharmacometrics (ACoP) Fort Lauderdale FL USA, October 2017.
AZRsim: An integrated platform for PKPD and QSP model simulation in drug development. Fox R, Chu L, Penland RC, Schmidt H, Pastoor D, Ali I, Helmlinger G, al-Huniti N. American Conference on Pharmacometrics (ACoP) Fort Lauderdale FL USA, October 2017.
Evaluation of immediate release exenatide effects on gastric motility and intestinal glucose absorption using a systems pharmacology model. Voronova V, Zhudenkov K, Penland RC, Boulton DW, Helmlinger G, Peskov K. Population Approach Group Europe (PAGE), Budapest Hungary, June 2017.
A Knowledge Management Solution for Pharmacometric Analysis. Fox R, Penland RC, al-Huniti N. American Conference on Pharmacometrics (ACoP) Bellevue WA USA, October 2016.
The impact of modelling and simulation in oncology: a survey of all drugs approved in oncology by the FDA 2005-2015. Edlund H, Lin T, Minchella K, Xu H, Penland RC, Masson E, al-Huniti N. American Conference on Pharmacometrics (ACoP) Bellevue WA USA, October 2016.
Novel orally swallowable IntelliCap® device to quantify regional drug absorption in human GI tract using diltiazem as model drug. Becker D, Zhang J, Heimbach T, Penland RC, Wanke C, Shimizu J. AAPS PharmSciTech, 15(6):1490-7, 2014.

Preclinical evaluation of cardiac sodium channel-mediated adverse effects. Erdemli G, Kim AM, Ju H, Springer C, Penland RC, Hoffmann PK. Society of Toxicology, 2013, accepted.
Cardiac safety implications of hNav1.5 blockade and a framework for preclinical evaluation. Erdemli G, Kim AM, Ju H, Springer C, Penland RC, Hoffmann PK. Frontiers in Pharmaceutical Medicine and Outcomes Research, 3(6): 1-9, 2012.
From particles to patients: An industrial perspective of the application of IVIVC for dose projection. Mueller-Zsigmondy M, Meier U, Saigne S, Penland RC, Heimbach T, Lin W, Li S, John E, Schuleit M, Becker D. accepted 8th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology. Istanbul, Turkey, March 2012.
Systems Toxicology Modeling for Prediction in Humans. Migliorini C, Lave T, Parrott NJ, Reddy M, Grimm HP, Penland RC, Soubret A, Helmlinger G, Georgieva A and Zuideveld KP. General, Applied and Systems Toxicology, 2011.
Models for integrative assessment of proarrhythmic risk in novel therapeutics. Penland RC. Invited lecture at Vertex Pharmaceuticals. July 2008.
Discovery and development of novel Kv1.5 inhibitors for atrial fibrillation. Penland RC. Ion Channel Targets, Boston, MA, 2006.
Bottino DC, Penland RC, Stamps A, Traebert M, Dumotier B, Georgieva A, Helmlinger G, Lett GS. Preclinical cardiac safety assessment of pharmaceutical compounds using an integrated systems-based computer model of the heart. Prog Biophys Mol Bio: Focused Issue on Integrative Physiology, 90(1), 2006.
Reconciling Discrepancies Between Channel-Level and Tissue-Level Cardiotoxicity Signals: A Model-Based Approach. Bottino D, Lett GS, Stamps A, Penland RC, Georgieva A, Helmlinger G, Hoffman P CHI World Pharmaceutical Congress, Philadelphia, PA, 2004.
Indirect observation of molecular-level drug effects from cell-level readouts: applications of Model-Based Assays. Bottino D, Lett GS, Kleinstein S, Cho C, Penland RC, Stamps A. Beyond Genome, Systems Biology, San Diego, CA, 2003.
Using in silico biology to facilitate drug development. Levin JM, Penland RC, Stamps AT, Cho CR. Novartis Found Symp, 247:222-238, 2002.
Penland RC, Harrild DM, Henriquez CS. Modeling impulse propagation and extracellular potential distributions in anisotropic cardiac tissue using a finite volume element discretization. Comput Vis Sci, 4:215-226, 2002.
Muzikant AL and Penland RC. Models for profiling the potential QT prolongation risk of drugs. Curr opin Drug Disc Dev, 5:127-135, 2002.
Harrild DM, Penland RC, Henriquez CS. A flexible method for simulating cardiac conduction in three-dimensional complex geometries. J Electrocard, 33:241-251, 2000.

Awards

Astrazeneca Early Clinical Development: Integrating Data to Inform R&D
Novartis SPOT Award for outstanding contributions
NSF Emerging Cardiovascular Technology Fellow
James B. Duke University Fellow
Department of Energy Computational Science Graduate Fellow
American Nuclear Society Graduate Fellow
North Carolina State University Award for Outstanding Scholarly Achievement
North Carolina State University Dean’s Fellow