AAPS-FDA workshop white paper: Microdialysis principles, application and regulatory perspectives

Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (mu D) is the only tool available that explicitly provides data on the extracellular space. Although mu D as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of mu D in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of mu D in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on mu D as a tool in drug research and development

Management criteria for Ficus insipida Willd. (Moraceae) in Amazonian white-water floodplain forests defined by tree-ring analysis

Ficus insipida Willd. (Moraceae) is a fast growing tree species of early successional stages in the Amazonian nutrient-rich white-water floodplains (várzea). The species is one of the most economically important low-density wood species in the community-based forest management project in the Mamirauá Sustainable Development Reserve (MSDR) in Central Amazonia, where timber species are managed using a polycyclic selection system with a minimum logging diameter (MLD) of 50 cm and a cutting cycle of 25 years. In this study we analyze the floristic composition, stand structure and forest regeneration of a natural 20 year-old stand at an early successional stage and we model tree growth of diameter, height and volume of F. inspida based on tree-ring analysis to define management criteria. The volume growth model indicates that the preferred period for logging should be at a tree age of 17 years when the current annual volume increment peaks. This age corresponds to a diameter of 55 cm, which would be an appropriate MLD. © INRA, EDP Sciences, 2007