Physiologically-Based Kinetic (PBK) Modelling Research at LJMU: PBK Webhub

At LJMU, we aim to provide a range of resources for users and developers of PBK models, curated by our researchers.

What is PBK modelling?

Physiologically-based pharmacokinetic (PBPK) modelling originated in drug development. It allows prediction of the concentration–time profile of a drug or drug candidate in blood or plasma as well as in individual organs of the body.

This detail is important because a drug’s effect depends on its concentration–time profile at the site of action. It is this internal exposure, rather than the administered dose, that determines whether an effect occurs.

The same principle applies in toxicology. Physiologically-based toxicokinetic (PBTK) models predict how toxic substances move through the body over time. They also help assess potential toxicological effects. Both PBPK and PBTK models follow the same principles. For this reason, they are often grouped together as physiologically-based kinetic (PBK) models.

These models treat an organism, such as a human, rat or fish, as a set of compartments representing organs. The compartments are connected by blood flow. Mathematical equations are then used to simulate the concentration of a drug or chemical of interest in the blood as it enters and leaves each organ.

From this the concentration-time profile of the chemical in individual organs (and blood / plasma) is predicted. These organ level concentration-time profiles can then be linked to effects.

The models use information about the chemical being studied, such as molecular weight and partition coefficients. They also use data about the organism, including organ volumes and blood flow rates. This information is combined to generate predictions of how the chemical behaves in the body.

Many PBK models have been developed for a wide range of chemicals including drugs, environmental pollutants and industrial chemicals. To build reliable models, a great deal of information is required. At LJMU we are collating resources that developers and users of PBK models may find useful.

These resources range from educational material and links to tutorials that introduce PBK model building, to resources for parameterising and recording PBK models. Links to the PBK Model Dataset (PMD), developed at LJMU, are also provided. This dataset provides basic information to hundreds of PBK models, published prior to 2021. This resource is currently being updated to include more recently published models.