Drugs and their targets have a complex relationship. This is especially true for large molecules like monoclonal antibodies. These big molecules often stick tightly to their targets. This leads to unusual behavior in how the body processes the drug. At low doses, the body clears these drugs faster than expected. This is because the drugs are stuck to their targets. This is what scientists call target-mediated drug disposition, or TMDD for short.

Small molecules, on the other hand, can have a different experience. When they bind to their targets, they can avoid being quickly removed from the body. This is because the target acts like a shield. It protects the drug from the body's clearance processes. This is the opposite of what happens with large molecules.

Scientists have found simple ways to describe these behaviors. They use a model called the TMDD model. This model has two main scenarios. One is when the drug binds very tightly to its target. The other is when the binding is weak. In the tight-binding scenario, the drug's behavior can be described using simple math. In the weak-binding scenario, things get a bit more complicated. The drug's behavior can be described using an equation called the Michaelis-Menten equation. This equation is famous in biology. It describes how enzymes work. But in this case, it's used to describe how drugs interact with their targets.

There's a twist, though. The Michaelis-Menten equation has a constant. This constant is important when the rates of target and drug-target complex elimination are different. Scientists had missed this factor before. It's important for understanding how drugs work in the body.

To understand how well a drug is working, scientists look at the ratio of free target to baseline. This is a measure of how much the drug is suppressing its target. Scientists have derived simple expressions for this ratio. They've also compared their approximations with data from both large and small molecules. This helps them understand how well their models work in real life.

Drugs and their targets have a complex relationship. This relationship can be described using simple math. But it's important to understand the details. The details can make a big difference in how drugs work in the body. This is especially true for large molecules like monoclonal antibodies. But it's also important for small molecules. Understanding these details can help scientists design better drugs.

NONLINEAR PHARMACOKINETICS

The Hidden Dance of Drugs and Targets

Continue reading...