The advances of nuclear medicine imaging instrumentation and radiopharmaceutical sciences allow their involvement in the developmental processes of therapeutic drugs. New chemical entities, meant as potential drugs, need to comply with the proof-of-principle. Tomographic imaging methods as PET, SPECT and CT have been used for small animal and human studies at an early stage of drug development....
BACKGROUND: Microdosing studies (human Phase 0) are used to select drug candidates for Phase I clinical trials on the basis of their pharmacokinetic properties, using subpharmacologic doses (maximum 100 microg). There are questions as to whether pharmacokinetic data obtained at these low doses will predict those at the clinically relevant dose. OBJECTIVE: To review the current literature on...
Drug development is an activity that is long, complex and expensive. In 2004, attrition in the drug development paradigm prompted the US Food and Drug Administration (FDA) to introduce its 'Critical Path' document, which highlighted the serious discordance between major scientific advances and limited drug development process. One issue addressed was that of microdosing. The concept of...
Positron emission tomography (PET)-microdosing comprises the administration of a carbon-11- or fluorine-18-labelled drug candidate to human subjects in order to describe the drug's concentration-time profile in body tissues targeted for treatment. As PET microdosing involves the administration of only microgram amounts of unlabelled drug, the potential toxicological risk to human subjects is...
The Food and Drug Administration (FDA) Critical Path Initiative as well as the European Medicines Agency Road Map to 2010 (ref. 2) call for opportunities for more efficient drug development. One of the initiatives that has emerged in this context is the elaboration through guidance of exploratory investigational new drugs (INDs)/clinical trial applications (CTAs). This article reviews the...
Abstract Microdosing of experimental therapeutics in humans offers a number of benefits to the drug development process. Microdosing, conducted under an exploratory Investigational New Drug (IND) application, entails administration of a sub‐pharmacological dose of a new chemical entity (NCE) that allows for early evaluation of human pharmacokinetics. Such information can be pivotal for: (1)...
Microdosing offers a faster and potentially less expensive approach to obtaining human in vivo PK data in early clinical drug development. It encompasses the use of pharmacologically inactive doses of test drug in the low microgram range along with ultrasensitive assay methods (PET, AMS) to assess human exposure in order to extrapolate the PK of higher, clinically more relevant doses, assuming...
OBJECTIVES: A volunteer trial was performed to compare the pharmacokinetics of 5 drugs--warfarin, ZK253 (Schering), diazepam, midazolam, and erythromycin--when administered at a microdose or pharmacologic dose. Each compound was chosen to represent a situation in which prediction of pharmacokinetics from either animal or in vitro studies (or both) was or is likely to be problematic. METHODS: In...
We present a new automated dosing system developed by the Institute for Automation of the University of Rostock, Germany. The new system is designed for the dosing of chemical liquids in the range of 50 μL–2.5 mL. It is integrated into a miniaturized reactor system to be used in the field of combinatorial synthesis. The reactor system can be pressurized up to 150 bar and tempered up to 200°C. A...
The realisation that new chemical entities under development as drug candidates fail in three of four cases in clinical trials, together with increased costs and increased demands of reducing preclinical animal experiments, have promoted concepts for improvement of early screening procedures in humans. Positron emission tomography (PET) is a non-invasive imaging technology, which makes it...