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Design and practical problems in population PK studies in the elderly

Brigitte Tranchand1, Silvy Laporte2

1 Pharmacokinetic Dpt, Centre Léon Bérard, Lyon, France ; 2 Clinical Pharmacology Dpt, University Hospital Saint-Etienne, France

Ageing is a highly complex and variable process, and old people do not age in a uniform way. Several parameters have to be taken into account before defining the age of the subject, as the chronological age or the biological age. Indeed, ageing is associated with multi-dimensional changes, such as alterations of physiological functions, comorbidities and poly-medications. This may result in modifications of the absorption, distribution, metabolism and excretion of the drugs. Therefore, the information obtained from "young" adults cannot be extrapolated to older patients.

Studies specific to the elderly must be performed in order to establish strategies for treating elderly patients on a scientific basis. As in adults, PK-PD studies are to be performed in healthy volunteers and/or in patients. PK studies in healthy elderly volunteers are often limited by recruitment problems: no existing national database, no financial interest... How can healthy elderly volunteers be found? What is meant by "healthy"? Are they old?

PK studies in patients will be discussed:

  • Firstly, studies including elderly patients in prospective phase II or phase III trials in adults; these rule out the problem of the number of samples (population approach), but raise the problem of finding the expected target population.
  • Secondly, studies including elderly patients in clinical routine practice; they raise the same problems as all other studies performed in clinical practice setting, i.e. make the medical team aware of the necessity of recording actual dosing and sampling times.
  • Then, studies specifically designed for elderly patients meet the problem of overusing the venous capital for daily nursing and, consequently, of finding enough blood and veins, even for sparse sampling designs.
  • Lastly, the particular case of anticancer agents, i.e studies specifically designed for geriatric oncology. Due to the lack of information on anticancer drugs in patients over 65, only intuitive dose reductions are used, which may significantly compromise the disease outcome. Using sparse sampling design, with adequate evaluation of the covariates (physiological ones and geriatric evaluation), we could expect to implement facilities for proposing optimal dosing and monitoring protocols for individual elderly patients in order to achieve targeted drug exposure.

In conclusion, the main difficulty is the lack of scientific references on optimal treatment-dosing in the elderly, as well as the lack of socio-economic data available in this population. Therefore, it is necessary to set up, and validate a referential in order to improve monitoring and therapy in elderly patients. This should help improve the quality of therapies and the management of the costs (direct and indirect) induced in this particular population. The best way is to undertake specific studies in the elderly.