Pharmacokinetics development principles

El-Kattan, A., Holliman, C., and Cohen, L.H., Quantitative bioanalysis in drug discovery and development Principles and applications, in Mass Spectrometry in Drug Metabolism and Pharmacokinetics, Ramanathan, R. (ed.), John Wiley Sons, Hoboken, NJ, 87, 2008. 

Mahmood, I. Interspecies pharmacokinetic scaling Principles, applications, and limitations. In Pharmacokinetics in drug development Clinical study design and analysis. (Bonate, P.L., and Howard, D., Eds.). AAPS Press, Alexandria, VA, 2004, pp. 423-444. 

A specific example showing the application of these principles within a development program for an ER dosage form is shown in Figures 3-5. A generalized pharmacokinetic model that can be used to support prototype selection is shown in... 

Reigner B, Williams PE, Patel 1, et al. An evaluation of the integration of pharmacokinetic and pharmacodynamics principles in clinical drug development. Experience within Hoffman La Roche. Clin Pharmacokinet 1997 33 142-52. 

Meibohm B, editor. Pharmacokinetics and pharmacodynamics of biotech drugs principles and case studies in drug development. Weinheim (Germany) Wiley-VCH 2006. 

The first tolerability studies in early clinical development always provide pharmacokinetic (PK) data over a considerable dose range. Especially the explorative first-in-man study with escalating single doses, or an explorative proof of principle study with escalating multiple doses provides a valuable basis for an exploratory assessment of dose linearity/ proportionality of drugs in humans. In addition such an assessment can directly help within the same study to optimize the dose selection and dose progression. Already in this early phase of the development, these data are going to support exposure-response relationships, and thus a potential submission (US FDA 2003, ICH E4 1994). 

The first tolerability studies early in a clinical development always provide pharmacokinetic (PK) data over a range of doses, mostly with a single-dose approach. In situations where an explorative proof of principle study... 

Rohatagi S, Martin N, Barrett J (2004) Pharmacoki-netic/pharmacodynamic modeling in drug development. In Krishna R (ed) Applications of pharmacokinetic principles in drug development. Kluwer Academic Publishers, New York... 

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