Japanese adopt microdose approach to ADME
Profiles says it has seen a surge in demand for its development
services in the Japanese market - with particular interest being
shown in its new human microdosing service.
Microdosing technology - in which only a very tiny amount of active substance is administered - can be used to start proof-of-concept studies early, and save both time and money by advancing only those candidates that are more likely to succeed.
As many as one in three drugs fail in Phase I clinical testing despite extensive preclinical screening of potential clinical candidates with a wide variety of in silico, in vitro, ex-vivo and animal models. A high proportion of these product failures can be attributed to unsuitable pharmacokinetic or inappropriate absorption, distribution, metabolism and excretion properties, which result in efficacy or safety issues in man, according to Pharmaceutical Profiles.
"Researchers and regulators are continually searching for faster and more cost-effective ways of obtaining early human bioavailability data, both safely and ethically," said the firm.
The recent advance of ultra-sensitive AMS (accelerator mass spectometry) has made it possible to undertake clinical studies in man using extremely low drug doses to obtain early PK and ADME data, notes PP, adding that these microgramme doses are up to 100 times below the level calculated to yield a pharmacological effect.
AMS is an extremely sensitive analytical technique with the ability to detect drugs down to attogramme or zeptogramme molar ranges. A key biomedical application of the technology is in the area of screening ADME studies.
Because these are undertaken in the ultimate target - man - they offer greater predictability versus preclinical animal and ex vivo models. Hence, human microdosing studies offer the promise of improved candidate selection and reduced attrition rates in formal clinical development.
Pharmaceutical Profiles executive chairman Ian Wilding commented: "with so many drug candidates exiting discovery and entering development, the task of choosing and then advancing the right molecules into the clinic has become more and more difficult and it seems that the Japanese market is looking at innovative new approaches."
