Department of Statistics Seminar
North Carolina State University

presents

David Giltinan

Genentech, Inc.

"Sensible Dosing When the 'Average Patient' Is a Myth: A Case Study in Population PK/PD Modeling"

ABSTRACT

Determining an appropriate dosing regimen for a new drug in clinical development is usually guided by the idea of a 'therapeutic window' for circulating drug concentration. The aim of dosing is to maintain the drug concentration in the bloodstream within a target range; concentrations which are too low may be subtherapeutic, while exceeding the upper limit of the range may lead to toxicity. Maintaining drug levels within the desired limits may be complicated by inter-subject variability in both the pharmacokinetic and the pharmacodynamic response to the drug. The former can result in large disparities in circulating drug levels in two subjects following the same dosage regimen, while the latter corresponds to differences in the concentration-effect relationship, so that a common target range may not be appropriate for all subjects.

Accurate characterization of inter-subject variation in pharmacokinetics and pharmacodynamics is thus essential to determine the appropriate dosing strategy. Typically, such characterization must be accomplished on the basis of infrequent, irregularly spaced, measurements of pharmacokinetic and pharmacodynamic response in subjects receiving the drug, though the number of subjects may be large. The nonlinear mixed effects model provides a useful framework for analyzing repeated measurement data of this type. Methods for inference in this model framework will be discussed and their application to investigating dosing strategies will be illustrated using data from a clinical study of a novel cardiovascular agent.

Friday, January 16, 1998

3:35 - 4:35 pm

206 Cox Hall

Refreshments will be served on the second floor of Dabney Hall (left of Room 222) at 3:00 pm.