12 drug discovery & development
(a) (b)
Fig. 2. Traditional (a) vs alternative rapid formulation manufacture and clinical evaluation model (b).
➠
By carrying out regional absorption studies in a small inhaled, for example) provides the opportunity to define
number of human volunteers, it is possible to map drug full pharmacokinetics, volume of distribution, absolute/
absorption windows (Fig. 4), understand solubility and relative bioavailability and establish the metabolic fate of
permeability issues and evaluate gastrointestinal (GI) a prospective drug in man.
metabolism and transport for a new drug. Drug-drug interactions, the routes and rates of
Microdosing of intravenous (iv) tracer 14 C-drug with elimination and potential ‘developability’ issues can also
simultaneous administration of non-labelled therapeutic be evaluated.
dose by the intended extravascular route (oral, dermal or These factors are usually assessed late in development.
The lack of a clear regulatory requirement for the data,
the need to manufacture an iv dose and the high cost of
conventional studies have combined to provide a barrier
to including this work in early development stages.
Now, innovative protocols and trial design allow
these issues to be addressed early, and with minimal
incremental cost. For example, by administering an iv
‘tracer’ microdose alongside ascending dose studies,
researchers can effectively ‘piggy-back’ a study using
Pharmaceutical Profiles ivMicrotracer on to their initial
clinical trials.
In a significant move, regulators have accepted that
tracer studies of iv formulations can go ahead without the
extensive preclinical safety package normally required to
Fig. 3. Combine intravenous microdosing and regional drug absorption support an intravenous regulatory submission.
studies to gain a complete picture. The Enterion capsule was designed Clinical studies at Pharmaceutical Profiles are
by Pharmaceutical Profiles’ scientists to provide a non-invasive means performed under Medicines and Healthcare Regulatory
to evaluate human regional drug absorption of all oral formulation Agency (MHRA) regulations.
types. It has been used in more than 100 clinical studies. Figures released for August 2008 show the average
Human regional absorption studies with enterion and ivmicrotracer in practice
e
nterion is a proprietary urine samples taken at regular intervals <100 nanoci. serial blood samples are
electromechanical device used by provide pharmacokinetic data, with results taken at regular intervals over 1–2 days
pharmaceutical profiles to deliver a drug providing absorption profiles for each and accelerator mass spectrometry
under test to specific regions of the gi region of the gi tract. (Ams) utilised to accurately measure the
tract. studies with ivmicrotracer typically 14c-drug levels in these blood samples.
By loading a formulation in an involve both oral and intravenous pharmaceutical profiles provides
enterion capsule, which incorporates a administration of the test drug at 1/100th additional time savings as a result of its
radiotracer port, progress through the gi of the pharmacological dose, or up ability to rapidly manufacture and evaluate
tract can be tracked in real time using to 100 micrograms, to 8–10 healthy new intravenous and oral formulations
images taken with a gamma camera. the volunteers. through onsite gmp facilities which are
capsule is triggered when it reaches its these microdoses contain trace situated alongside the company’s gcp
target, releasing the dose form. Blood and amounts of 14c-radiolabelled drug, usually clinical unit. u
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