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A complementary article to this review that places emphasis on issues related to metabolic drug–drug interactions.
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Essential reading for those interested in clinical trial simulations.
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Jackson, P. R., Tucker, G. T., Lennard, M. S. & Woods, H. F. Polymorphic drug oxidation: pharmacokinetic basis and comparison of experimental indices. Br. J. Clin. Pharmacol. 22, 541–550 (1986).
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A practical example illustrating the importance of attention to variability.
Rostami-Hodjegan, A., Jackson, P. R. & Tucker, G. T. Sensitivity of indirect metrics for assessing 'rate' in bioequivalence studies — moving the 'goalposts' or changing the 'game'. J. Pharm. Sci. 83, 1554–1557 (1994).
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MacDonald, A. J., Rostami-Hodjegan, A., Tucker, G. T. & Linkens, D. A. Analysis of solvent central nervous system toxicity and ethanol interactions using a human population physiologically based kinetic and dynamic model. Regul. Toxicol. Pharmacol. 35, 165–176 (2002).
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An early indication of the need to incorporate variability in physiologically based pharmacokinetic models, though the clearance component did not include biological sources of variation.
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A classic text for those who wish to understand the link between in vitro and in vivo metabolism in the liver.
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An essential reference for anyone seeking information on anatomical and physiological changes from childhood to adulthood. The implications of each element are described with examples. The report also identifies the paucity of data in certain areas.
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A comprehensive review of the issues involved in extrapolating in vitro data on clearance to clinical studies.
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A guide to using information on drug metabolizing enzymes to assess the pharmacokinetic and pharmacodynamic consequences of genetic variation.
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An early comprehensive report on issues related to assessing drug–drug interactions using in vitro systems.
Food and Drug Administration (FDA). Guidance for industry: drug interaction studies — study design, data analysis, and implications for dosing and labeling. FDA web site [online], (2006).
A must-read guide that provides an insight into the current thinking of regulatory authorities on issues related to the use of in vitro systems as an alternative to in vivo studies, or as a framework for deciding the type and design of studies to carry out.
Yang, J. et al. Implications of mechanism-based inhibition of CYP2D6 for the pharmacokinetics and toxicity of MDMA. J. Psychopharmacol. 20, 842–849 (2006).
Howgate, E. M., Rowland Yeo, K., Proctor, N. J., Tucker, G. T. & Rostami Hodjegan, A. Prediction of in vivo drug clearance from in vitro data. I: impact of inter-individual variability. Xenobiotica. 36, 473–497 (2006).