Delays in PKPD

ICON plc. April 12th 2019, Columbia, Maryland, USA

Modeling Delays in Pharmacokinetics and Pharmacodynamics

The course will provide an overview of biological systems exhibiting delays, concepts of lifespan driven pharmacodynamic response, modeling of cell maturation, and nonlinear mixed effect lifespan models. Delay differential equations (DDEs) will be introduced and implemented in NONMEM pre-release version 7.5. The course will consist of both lectures and hands-on computer exercises. Source codes for DDE based PK/PD models and data will be provided to the participants.


Business Training Center, 6751 Columbia Gateway Drive, Columbia MD 21046, USA


Industry - $700/per day

Academia/Government - $500/per day

Student - $300/day

A discount of 15% is available to groups of 3 or more participants from the same organization.

Contact Lisa Wilhelm-Lear at for more information and to register.

Deadline for registration is: April 4, 2019


Instructors are members of Pharmacodynamic Systems with Delays Research Group

Wojciech Krzyzanski, PhD, MA. Associate Professor at Department of Pharmaceutical Sciences, University at Buffalo. Holds PhD in applied mathematics and MA in pharmacology. Research focus on pharmacokinetics and pharmacodynamics of hematopoietic growth factors and pharmacometrics.

Gilbert Koch, PhD. Gilbert Koch holds a PhD in applied mathematics. He worked as Postdoctoral Associate at the Department of Pharmaceutical Sciences, University at Buffalo and recently joined the Pediatric Pharmacology Group at the University Children´s Hospital in Basel as Senior Research Fellow. His research focus is on delay/lifespan modeling, anti-cancer effects in combination therapy, modeling in pediatric drug development and rare diseases, and target mediated drug disposition with drug-drug interaction.

Robert J. Bauer, PhD. Robert Bauer holds a PhD. in Pharmacology. He heads the Pharmacometrics R&D department at ICON Plc, Gaithersburg, MD., where he and his group maintain the population analysis software NONMEM®, incorporating leading edge algorithms in pharmacometrics. Dr. Bauer’s focus is on developing and implementing mathematical and statistical algorithms for biomedical problems.


8:00am - 8:10am Introduction

8:10am - 8:50am Biological systems exhibiting delays

                    • Hematopoietic cascade
                    • Immune system response
                    • Apoptotic cancer cells

8:50am - 9:20 am Concept of lifespan driven pharmacodynamic response

                    • Lifespan controlled cell loss
                    • Point distributed lifespans
                    • Lifespan PD models with delays

9:20am - 10:00am Introduction to delay differential equations in PK/PD

                    • Overview of DDE systems
                    • Categories of DDE models

10:00am - 10:20am Coffee break

10:20am - 11:10am Hands-on I

                    • Introduction to ADVAN16 for solving DDEs
                    • Implementation in NONMEM of PKPD models with DDEs
                    • Simulation and estimation of parameters in PKPD models with delays

11:10am - 11:50am Basic lifespan based indirect response models

                    • Drug effect on response production
                    • Drug effect on lifespan distribution

11:50am - 1:00pm Lunch break

1:00pm - 1:50pm Hands-on II

                    • Coding basic lifespan indirect model III
                    • Simulation of repsones for varying dose and TR

1:50pm - 2:20pm Transit compartment models

                    • Transit compartment model properties
                    • Signal transduction
                    • Cell maturation and senscence

2:20pm - 3:10 pm Hands-on III

                    • Rheumatoid arthritis model
                    • Estimation of parameters for escalating single dose data

3:10pm - 3:30pm Coffee break

3:30pm - 4:10pm Lifespan models of hematopoietic systems


                    • PD models for rHuEPO, PegTPO
                    • Hematological toxicities and rHu-G-CSF

4:10pm - 5:00pm Hands-on IV

                    • Population model of rHuEPO effect on hemoglobin
                    • Estimation of population parameters for hemoglobin response

5:00pm - 5:05pm Final comments and remarks