Prof Geoffrey Tucker

Professor Emeritus, Academic Unit of Clinical Pharmacology, University of Sheffield;
Chairman of Simcyp Ltd, Sheffield UK.

Research Interests

Over 350 full papers and 300 refereed abstracts in the areas of clinical and theoretical pharmacokinetics/pharmacodynamics, human drug metabolism, pharmacogenetics and the pharmacology of drugs used in anaesthesia.

Activities and Distinctions

Highly Cited Author (Pharmacology) - Institute of Scientific Information (ISI).

Councillor - International Society for the Study of Xenobiotics (ISSX) (1988-91; 2004-).

Vice-President, International Pharmaceutical Federation (FIP) (2008-).

Founder Member and Elder of the African Society for Drug Metabolism and Development.

Visiting Professor at the Universities of Harvard, Cincinnati, Otago and the US Food and Drug Administration (FDA) .

http://www.shef.ac.uk/medicine/staff/tucker.html

PREDICTING PHARMACOKINETICS FROM THE ‘BOTTOM UP'

G.T.Tucker

        There are several approaches to predicting pharmacokinetic behaviour in humans, based on QSAR, allometry and physiologically-based pharmacokinetic modelling (PBPK). Of these, only PBPK modelling allows direct prediction of full concentration – time profiles at different sites, and variability in such profiles as a consequence of differences in demography, physiology, genetics and disease. Assessment of the effect of the many variables likely to affect PK behaviour from independent pieces of information represents a prospective ‘bottom up' approach, in contrast to the ‘top down' approach which attempts to identify co-variates retrospectively from actual plasma drug concentration data (population PK). While these two approaches are not mutually exclusive, the first has significant potential to inform the design and interpretation of the latter. The ‘bottom up' approach incorporates in vitro information on drug disposition in attempting to account for the interplay between enzymes and transporters, competitive and time-dependent irreversible enzyme inhibition, the impact of genetic polymorphism and combined enzyme inhibition and induction. The development of algorithms to piece together elements of drug absorption, distribution and elimination will be reviewed and illustrated with examples of their application in understanding the extremes of PK risk as a function of age, ethnicity and disease.