PK/PD model

PK/PD modeling (pharmacokinetic/pharmacodynamic modeling) (alternatively abbreviated as PKPD^[1] or PK-PD^[2] modeling) is a technique that combines the two classical pharmacologic disciplines of pharmacokinetics and pharmacodynamics.^[3] It integrates a pharmacokinetic and a pharmacodynamic model component into one set of mathematical expressions that allows the description of the time course of effect intensity in response to administration of a drug dose. PK/PD modeling is related to the field of pharmacometrics.

Central to PK/PD models is the concentration-effect or exposure-response relationship.^[4] A variety of PK/PD modeling approaches exist to describe exposure-response relationships. PK/PD relationships can be described by simple equations such as linear model, Emax model or sigmoid Emax model.^[5] However, if a delay is observed between the drug administration and the drug effect, a temporal dissociation needs to be taken into account and more complex models exist:^[6][7]

• Direct vs Indirect link PK/PD models
• Direct vs Indirect response PK/PD models^[8]
• Time variant vs time invariant
• Cell lifespan models
• Complex response models

PK/PD modeling has its importance at each step of the drug development^[9][10] and it has shown its usefulness in many diseases.^[11] The Food and Drug Administration also provides guidances for Industry to recommend how exposure-response studies should be performed.^[12]