The population approach: rationale, methods, and applications in clinical pharmacology and drug development

Variation in the response of individual patients to drugs is a matter of major concern in drug evaluation and therapy (Rowland et al. 1985). Since the seminal paper in 1972 (Sheiner et al. 1972), followed by its first application to digoxin 5 years later (Sheiner et al. 1977) and the release of software (Beal and Sheiner 1980), “population pharmacokinetics” has been an area of active research in clinical pharmacology, despite scepticism among many pharmacokineticists, most clinicians, and, with rare exceptions, general indifference or even antagonism within the pharmaceutical industry.