What's the difference between toxicokinetics and toxicodynamics?

Toxicokinetics (TK) and toxicodynamics (TD) are two basic but separate concepts in toxicology that are interrelated and can be used to describe how a toxin behaves in the body and what effects it has.

Toxicokinetics refers to how the body processes a toxin. The principles of toxicokinetics include how the toxin is absorbed, where it goes in the body, how it is metabolised, and how it is excreted (ADME). In other terms, TK is about the kinetics of a chemical entering the body, its distribution in the body, its breakdown, and its final excretion in urine and/or feces. It explains how quickly a drug is absorbed and distributed throughout the body. For example, in acetaminophen (paracetamol) overdose, toxicokinetics can help us estimate how much is converted to the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI), and how long the drug remains in the system.

Toxicodynamics refers to the effects of the toxin on the body. It can describe the mechanism of action at the cellular or molecular level (e.g., receptor binding, enzyme inhibition, cellular damage). For example, in organophosphate poisoning, toxicodynamics helps us understand that inhibition of acetylcholinesterase leads to excessive acetylcholine (ACh), causing cholinergic toxicity—regardless of the dose or route of exposure.

Understanding one without the other can lead to serious clinical or regulatory mistakes. For example, if someone at risk of colchicine poisoning (from a plant, medications, etc.) only considers TK and sees that plasma levels are significantly declining from a high level to potentially a low or normal level, they may see this as a positive sign and miss out on considering the toxicodynamic. Toxicodynamically, colchicine has a long duration of action via its ability to disrupt the microtubules inside cells and lead to delayed multiorgan failure from a single exposure. So even if plasma levels appear low, the toxic effects can still be severe and continue to worsen. Misunderstanding either one of those principles could lead to a clinician deciding that monitoring should diminish, and the patient is not seriously sick, or premature discharge from the acute care facility.

Today, toxicokinetics and toxicodynamics are both relevant in regulatory science and drug development. TK studies help the drug and regulatory scientists determine safe dosing and timing, while TD studies help determine what the target organ is and how it is injured. Both data TK and TD are being utilized during preclinical studies for regulatory application; they can be utilized in risk assessment models and while developing early phase clinical trials. For regulatory agencies and the data generated, they will use both TK and TD data to consider the safety of a compound produced, what levels are considered acceptable exposure, and what information is needed to ensure safe use in both human and animal cases

In summary, toxicokinetics tells us how much of a toxin has reached the body and for how long, while toxicodynamics tells us what happens when it reaches the body. Both concepts are necessary to fully understand if we are to provide an accurate and defensible risk assessment, for effective treatment, and responsible decision making, when it comes to regulatory pathways.