Pharmacokineticpharmacodynamic

Pharmacokineticpharmacodynamic (PKPD) is the integrated analysis of the relationship between drug exposure (pharmacokinetics) and drug effect (pharmacodynamics). The goal is to quantify how concentrations achieved in the body translate into therapeutic or adverse effects over time, and to use that information to optimize dosing.

Pharmacokinetics describes how the body handles a drug: absorption, distribution, metabolism, and elimination. It defines the concentration-time profile in plasma and tissues using compartmental or noncompartmental models, and it is influenced by formulation, route of administration, organ function, and patient characteristics.

Pharmacodynamics describes what the drug does to the body: the mechanism of action, receptor interactions, and the relationship between concentration and effect. Effects are characterized by onset, duration, maximum effect, potency (EC50), and safety margins. Some drugs show direct effects; others have delayed or indirect effects.

PKPD modeling links exposure to response. Common models include the Emax model for maximal effect with EC50 and Hill coefficient, and indirect response models for effects mediated by synthesis or degradation of endogenous mediators. Time delays and hysteresis can be addressed with link models, transit compartments, or reversible binding.

Applications include dose selection, regimen design, and personalized medicine through population PK/PD analyses, Bayesian forecasting, and simulations. Challenges include variability between individuals, time delays between concentration and effect, and translating surrogate endpoints to clinical outcomes.