Delays in PKPD

ACoP 11 October 4, 2020, Aurora, CO, USA

Modeling Delays in Pharmacokinetics and Pharmacodynamics

Pharmacodynamic Systems with Delays Research Group will present a one day workshop on Modeling Delays in Pharmacokinetics and Pharmacodynamics using NONMEM on Sunday the 4th of October. The course will provide an overview of biological systems exhibiting delays, concepts of lifespan driven pharmacodynamic response, modeling of cell maturation, transduction delays, 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 code for DDE based PK/PD models and data will be provided to the participants. For more information contact


Gaylord Rockies Resort & Convention Center

Aurora, CO, USA


Registration can be made via the ACoP11 website . Please register ASAP in view of the limited course capacity of 30 participants. Confirmation of registration will be returned upon receipt, together with an invoice for the course fee. Registration will not be final until payment is received.


Registration fees are 175 USD for students, 350 USD for academia/government, and 700 USD for a regular registration. This includes course documentation, mid-session refreshments and lunch.


Cancellations with a full refund may be made until September 20, 2020. No refund is possible on cancellations received after this date. Substitutions may be made at any time.


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 holds a PhD in applied mathematics and is a senior research fellow in modeling and simulation at the University Children’s Hospital Basel, Switzerland. He has more than 12 years of experience in pharmacokinetic and pharmacodynamic modeling. His research topics are modeling in (preterm) neonates and infants, computation of optimal dosing schedules, machine learning approaches, drug-drug interaction modeling, and the development of app-based solutions for clinicians.

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.

Johannes Schropp, PhD. Professor at Department of Mathematics and Statistics, University of Konstanz. Research focus on PK/PD modeling and numerics of dynamical systems.


9:00am - 9:10am Introduction

9:10am - 9:50am Biological systems exhibiting delays

                    • Hematopoietic cascade
                    • Immune system response
                    • Apoptotic cancer cells

9:50am - 10:30am Concept of lifespan driven pharmacodynamic response

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

10:30am - 10:50am Coffee break

10:50am - 11:30am Introduction to delay differential equations in PK/PD

                    • Overview of DDE systems
                    • Categories of DDE models

11:30am - 12:30am 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

12:30am - 1:30pm Lunch break

1:30am - 2:10pm Basic lifespan based indirect response models

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

2:10pm - 2:50pm Hands-on II

                    • Coding basic lifespan indirect model III
                    • Simulation of repsones for varying dose and TR
                    • Estimation of parameters for escalating single dose data

2:50pm - 3:20pm Transit compartment models

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

3:20pm - 3:40pm Coffee break

3:40pm - 4:20 pm Hands-on III

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

4:20pm - 5:00pm Lifespan models of hematopoietic systems

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

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