Model-informed precision dosing (MIPD) is increasingly used to translate population pharmacokinetic, physiologically based pharmacokinetic, pharmacodynamic, biomarker, and therapeutic drug-monitoring information into patient-specific dose decisions. Its value is particularly compelling in patients whose physiology departs from that represented by conventional dosing studies, yet “special population” is an imprecise dosing construct. Childhood, ageing, pregnancy, renal or hepatic dysfunction, obesity, and critical illness alter different determinants of exposure and response, often dynamically and with drug-specific consequences. This State-of-the-Art Review examines how these sources of variability should be represented, transferred, updated, and interpreted within MIPD. We propose that population membership should be treated as a prior description of physiological state rather than a direct dose instruction. Four questions organize the synthesis: whether relevant physiology is represented, whether the model transports to the clinical state, whether individual observations can update the prior prediction, and whether the resulting recommendation improves a decision-relevant endpoint. This separation prevents model fit, exposure prediction, target attainment, and clinical benefit from being treated as interchangeable evidence. Across special populations, precision dosing is therefore best understood as a conditional inference process whose credibility depends on physiology, model validity, informative observations, and the clinical horizon over which the dose decision is made.
IJPRAS
