How to Build a PK-Sim Model with Explicit Albumin-Binding Ligand and Turnover

Learn step-by-step how to create a pharmacokinetic (PK) simulation model with an albumin-binding ligand, including explicit albumin turnover and binding, using PK-Sim and MOBI. This guide covers molecule setup, clearance processes, module integration, and parameter adjustments for accurate albumin-ligand complex modeling.

March 13, 2026 By Wilbert de Witte

In this guide, we'll learn how to build a pharmacokinetic model with an albumin-binding ligand, including explicit albumin turnover and binding. We will start with a basic PK-Sim model for large molecules, add necessary clearance processes, and set up simulations with both the ligand and its complex. The guide will also cover how to integrate modules for FcRn recycling and albumin, rename molecules for consistency, and adjust parameters for different scenarios.

Let's get started

In this manual, I will demonstrate how to build a model with an albumin-binding ligand, including explicit albumin turnover and binding. We start with a PK sim model that is standard for any large molecule model. We have two molecules here.

A complex, which is the albumin-ligand complex, but you can give it any name. Then there's the ligand.

Step #1: Click on "Ligand" — Click on "Ligand"

Both of these are large molecules, so it's important to make sure the "is small molecule" box is unchecked.

Step #2: Click on "ADME" — Click on "ADME"

Both of these molecules also have a renal clearance process. It's important that the renal clearance process is present. The parameters are not very important. Those can be changed easily later, but adding a renal clearance process is more complicated if done afterward. Next, we add a simulation that includes both molecules and an administration protocol for each.

The dose can be zero, as we don't need it in the simulation. We can change this later as well. Most importantly, both have an administration protocol. The albumin ligand should not have a zero dose. The albumin-ligand complex is typically not dosed. That can be zero. Then we send this simulation to MOBI by right-clicking and selecting Send to MOBI. Next, we switch to the simulation open in MOBI.

Step #3: Right-click on "L5 + C5" — Right-click on "L5 + C5"

That is the simulation here, which contains all the building blocks. You can also see the molecules and their FcRn complexes.

We don't need to change anything there, but we add two new modules: the FcRn recycling module we developed before, and now the new albumin module.

We need to have both and then build a new simulation that includes both. Before we proceed, we need to do some renaming.

We look at the molecule building block for the FcRn module and see some molecules with different names. It also states that this molecule building block is only for renaming FcRn complexes.

Let's look at the molecules in our actual PK Sim building block.

It’s the FcRn complex that we want to make sure is in our FcRn module, and the same applies to the ligand FcRn complex.

We can either copy these names or retype them.

First, open the molecule building block by double-clicking it. Then, rename the FcRn complex to either "ligand" or "complex."

Step #9: Double-click on the molecules building block — Double-click on the molecules building block

Step #10: Click on "- FcRn_Complex" — Click on "- FcRn_Complex"

Step #11: Right-click on "- FcRn_Complex" — Right-click on "- FcRn_Complex"

Step #12: Click on "Rename..." — Click on "Rename..."

Let's call this one the FcRn complex.

Type "Complex"

Okay. If you get this pop-up, you have typed the name correctly. If you don't get it, you are probably making some spelling mistakes. That's a good quality check.

The other FcRn complex will now be renamed to ligand FcRn complex.

Step #16: Click on "WT IgG - FcRn_Complex" — Click on "WT IgG - FcRn_Complex"

Step #17: Right-click on "WT IgG - FcRn_Complex" — Right-click on "WT IgG - FcRn_Complex"

Step #18: Click on "Rename ..." — Click on "Rename ..."

We will get the pop-up again and confirm that it is okay.

Type "Ligand"

As you see here, the molecules building block is only for renaming the FcRn complexes. We don't need to worry about the other molecules, and we can now remove the entire building block.

Step #22: Right-click on "Molecules - only for renaming FcRn complexes !" — Right-click on "Molecules - only for renaming FcRn complexes !"

Step #23: Click on "Delete..." — Click on "Delete..."

Step #24: Click on "Yes" — Click on "Yes"

It's done. Now we do a similar process for the albumin module.

Here, if we look at the molecules and open the molecules building book, we see the albumin, which can and should stay the same name.

Step #28: Double-click on "Molecules" — Double-click on "Molecules"

Step #29: Right-click on "Albumin_Ligand _RENAME_and_REMOVE" — Right-click on "Albumin_Ligand _RENAME_and_REMOVE"

We can rename it, but it's not necessary. Albumin ligand says to rename and remove, so we will do that. Name it the same as our ligand molecule in PK-Sim, which is just "ligand" in this example.

Step #30: Click on "Rename..." — Click on "Rename..."

Again, we get all the renaming that results from this and prove it. Then, there is the complex, which we will also rename to "complex."

Step #33: Right-click on "Albumin_Ligand_Complex_RENAME_and_REMOVE" — Right-click on "Albumin_Ligand_Complex_RENAME_and_REMOVE"

Step #34: Click on "Rename..." — Click on "Rename..."

Type "Complex"

Okay.

Both of these molecules had "rename" and "remove" in their names, so we are also going to remove them.

Step #38: Right-click on "Ligand" — Right-click on "Ligand"

Step #39: Click on "Delete..." — Click on "Delete..."

Step #40: Click on "Yes" — Click on "Yes"

Step #41: Right-click on "Complex" — Right-click on "Complex"

Step #42: Click on "Delete..." — Click on "Delete..."

Now they are gone.

Step #43: Click on "Yes" — Click on "Yes"

Now we are ready to build our new simulation.

Create a simulation, add both modules, and run it.

Step #44: Right-click on "Simulations" — Right-click on "Simulations"

Step #45: Click on "Create Simulation" — Click on "Create Simulation"

Step #46: Click on "L5 + C5" — Click on "L5 + C5"

Step #47: Click on "Add" — Click on "Add"

Type "New"

Step #51: Click on "Next" — Click on "Next"

Now, we are building the simulation with all the required molecules, reactions, and processes needed.

Step #53: Click on "New" — Click on "New"

We get the new simulation.

Run it.

Step #54: Click on "Run" — Click on "Run"

As you can see, we have a molecule with some clearance and normal pharmacokinetics. We see that there are some processes involved that we can examine. Plasma albumin synthesis and gastrointestinal tract clearance of albumin.

There is free ligand in plasma at very low concentrations, and the complex in plasma is present at much higher concentrations. This is due to the affinity and albumin concentrations, which cause a significant difference between the concentrations of these molecules.

Step #56: Click on "Parameters" — Click on "Parameters"

Now we can also look at the parameters.

Step #57: Click on "Organism" — Click on "Organism"

For albumin, the list of parameters for the molecule includes the reference plasma concentration. This value can be adjusted for a diseased individual or a different species.

Step #59: Click on "43.00 g /" — Click on "43.00 g /"

It is important that this is used only for the initial condition. It doesn't change the actual steady-state concentration, but we can adjust it to a lower value if we have that reference value. For example, we can set it to 20, and it will not update the initial concentration.

Type "20 + Enter"

Step #62: Click on "Results" — Click on "Results"

I won't rerun the simulation. Instead, I'll show you right away how it should be done if you want to adjust the concentration. We need to find the albumin synthesis rate constant.

Step #63: Click on "Parameters" — Click on "Parameters"

Step #64: Double-click on "Albumin Synthesis" — Double-click on "Albumin Synthesis"

Step #65: Click on "1.00" — Click on "1.00"

That one has a factor where we can say we want approximately half of that, or maybe 40%, which is more similar to what I did.

Type "0.40 + Enter"

Step #67: Click on "Results" — Click on "Results"

Now we can rerun the concentration. We should also look at the albumin concentration.

I will add that here.

I want the plasma concentration of peripheral venous blood.

Step #70: Double-click here — Double-click here

There we go. We run the simulation and examine the albumin concentration, which is not immediately visible here.

Step #73: Click on "▸ Category :" — Click on "▸ Category :"

Step #76: Click on "Chart Options" — Click on "Chart Options"

Step #77: Click on "RightInside" — Click on "RightInside"

There it is, all the way on top.

Step #78: Click on "BottomInside" — Click on "BottomInside"

You can see it is now in a different unit, allowing us to compare it with the reference value we set.

Step #79: Click on "Curve and Axis Settings" — Click on "Curve and Axis Settings"

So it's about 20...

I think it was gram per liter, so I will change it here.

It's about 20 grams per liter, which we set by reducing the census rate by approximately 60%.

Step #80: Click on " g/l" — Click on " g/l"

That's how simulations can be built, used, and optimized. These two parameters that we changed can also be fitted. With that, all the information is in place to redo this for your own project and set up any explicit albumin binding simulations.