PKPDmalleissa

PKPDmalleissa is a theoretical framework proposed in speculative pharmacology to extend standard pharmacokinetic–pharmacodynamic (PKPD) modeling by explicitly incorporating malleability in the exposure–response relationship. It introduces a malleability factor that varies with time and context and modulates how drug exposure translates into effect, aiming to reflect adaptive physiology, disease evolution, and external influences on drug action. The term is not a standard term in mainstream pharmacology and is largely found in educational or conceptual discussions and fiction. It is used to illustrate how dynamic biological systems can alter PK or PD independently of changes in drug concentration.

Model structure typically adds a malleability state variable or time-varying covariate to PK or PD equations. The approach often employs differential equations or state-space models and can include feedback where drug effects influence physiology that, in turn, alters exposure or sensitivity. Such a framework can also accommodate interactions among multiple factors, such as age, disease progression, or concomitant medications.

Potential applications include teaching about adaptive drug responses, exploratory simulations for personalized medicine, and sensitivity analyses of how comorbidities or co-medications might shift dose–response relationships. Limitations include lack of validation, increased data requirements, potential identifiability issues, and the risk of overfitting when malleability is given too many parameters.

Related topics include pharmacokinetics, pharmacodynamics, PK/PD modeling, systems pharmacology, and physiologically based pharmacokinetic modeling.