Xceleron CSO, Dr Graham Lappin, is to present at the DIA’s annual meeting, being held June 24-28, 2012, in Philadelphia, PA.
Graham’s presentation will be part of a session entitled “Microdosing: Past Experience and Future Role in Translational Medicine” to be chaired by Tal Burt of the Duke Clinical Research Unit.
This conference provides an invaluable forum for professionals involved in the discovery, development, and life-cycle management of pharmaceuticals, medical devices, and related products, including discussion of current issues related to translational medicine, drug efficacy and development.
The concept of microdosing, where preliminary human pharmacokinetic data are obtained using sub-pharmacologic amounts of drug administered to human volunteers prior to Phase-1 studies, has been around for over a decade. It started as nothing more than a concept with little supporting–data in a review in Nature Drug Discovery in 2003 (Lappin and Garner Nat Drug Discov 2(3), 233-40). There are now however, data for around 30 drugs in the public domain comparing a microdose with a therapeutic dose and the regulatory framework to allow a microdose study to take place is well established. Many microdose studies have been performed, although it is difficult to estimate how many as much of the data remains unpublished due to the commercially sensitive nature of the information. The question from the beginning was how well a microdose might predict the pharmacokinetics at higher therapeutic doses? The current database, consisting of around 30 drugs is about 80% predictive (based on a 2-fold range, generally accepted in allometry).
Microdosing therefore, does seem to be showing utility and would appear to be more predictive than the more traditional methods such as allometry and PK-PD modelling, although care has to be taken when comparing the outcomes of the various techniques. Where pharmacokinetic non-linearity does occur in microdosing, primarily with oral dosing, the reasons for these non-linearities are now becoming understood. The technique is also proving useful in the study of drug transporters. The uptake of microdosing studies within the industry has nevertheless been slow and they have mostly been used in specific circumstances.
The ten year history of microdosing will be reviewed, including the two major human studies, the so called CREAM Trial and EUMAPP. The drivers for conducting microdosing studies and where they have been useful will be examined. More recently, the concept of microdosing has been widened to look at drug-drug interactions (DDI) and technologies such as Accelerator Mass Spectrometry have been combined with Positron Emission Tomography. Microdosing also provides an opportunity to readily obtain intravenous data early in humans, which can have wide implications downstream in formulation, bioavailability and potential DDIs. There appears to be a revival of interest in microdose studies as the application of the technique widens. We will have to wait and see if the revival really takes hold.
To download a copy of this presentation, please click here: Link
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