Pharmacology of cytotoxic agents: a helpful tool for building dose adjustment guidelines in the elderly

Aging is associated with multidimensional changes, including alterations in physiological functions, co-morbidities and poly-medications. These changes may lead to modifications in the absorption, distribution, metabolism and excretion of drugs. The lack of a scientific basis for optimal drug dosing in the elderly is a major problem. The development and validation of guidelines are therefore essential to improve treatment administration and monitoring in elderly patients. Even though it has been widely demonstrated that standard therapies used in adults may be of great benefit in the elderly, there may be a higher incidence of toxicity. This could be avoided by using dosage individualization based on a sound knowledge of the physiological factors implicated in the pharmacokinetic (PK) characteristics of the drugs administered and in their observed pharmacodynamic (PD) effects in each patient. The so-called "population modeling" approach renders such studies feasible by allowing the analysis of PK-PD relationships from sparse observational data.