Should a pharmacokinetic model be more than its data?

Abstract

Pharmacokinetic model development gains its deeper value not from adequately describing observed data but from demonstrating reliable extrapolation beyond dataset-specific patterns. This principle is especially critical in paediatric drug development, where adult data often guide subsequent studies. Modelling strategies accounting for allometry and maturation help ensure that predictions remain plausible across populations. A recent study in the British Journal of Anaesthesia illustrates this by showing that fixed allometric scaling combined with a maturation function produced paediatric ciprofol predictions that extrapolated plausibly to adults, whereas estimating allometric exponents alone resulted in unrealistically high clearance values that could have translated into inappropriate dosing recommendations. Extrapolation grounded in physiological principles aligns with regulatory requirements and supports safe, evidence-based dosing. Extrapolation performance is therefore a critical indicator of mechanistic credibility, revealing whether a model can provide predictions across populations to reliably inform dosing.