Early clinical development:
Microdose experiences
Dr. Lloyd Stevens, Principal Scientist, Pharmaceutical Profiles, UK
Microdose and 14C-tracer pharmacokinetic studies
are now finding wider application for compound selection and early clinical evaluation. This presentation is based on practical experience and
will provide a comprehensive review of the logistics of running a microdosing study and the ability to identify potential “drugability” or “developability” issues as early as possible in the clinical development process. |
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Early Human PK: Enhanced Phase I
and Metabolite Profiling
Dr. Colin Garner, CEO,
Xceleron Inc, US
By using smart study design and 14C-tracer technology, Enhanced Phase I Studies allow information such as Mass Balance, Metabolite Profiling and Human IV PK to be obtained from a Phase I study with little additional cost. This presentation will give
an overview of the usefulness of these studies and the information that can be obtained, focussing on Human Metabolite Profiling and it’s importance in early clinical development. |
| The discussion will focus on: |
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Selection, de-selection and target product profile drivers of study design |
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Provision of 14C-API and associated GMP manufacture of appropriate formulations |
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Examples of pharmacokinetic output
and interpretation |
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Utility of IV-microdosing to define absolute bioavai ability and identify the cause of poor and variable bioavailability early in clinical development |
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To register for the symposium
please click here > |
Join us after the symposium for drinks and canapés at the Delta Hotel Bar.
We hope that you can join us and look forward to meeting you in Québec. |
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A pharmacokinetic evaluation of five H1 antagonists after an oral and intravenous microdose to human subjects Dr. Ajay Madan, Neurocrine Biosciences Inc, US
Pharmacokinetics of five H1 receptor antagonists, namely, NBI1, NBI-2, NBI-3, NBI-4 and diphenhydramine were evaluated in human volunteers after a single oral and intravenous (IV) microdose (0.1 mg). Blood samples were collected up to 48 hours, and the parent compound in the plasma extract was quantified by HPLC and Accelerator Mass Spectrometry. The mean clearance (CL), volume of distribution (Vd) and apparent terminal elimination half-life (t1/2) of diphenhydramine after an IV microdose were 24.0 L/h, 313 L and 9.0 h, and the oral Cmax
and AUC0-inf were 0.191 ng/mL and 1.58 ng.h/mL, respectively. These data were consistent with previously published diphenhydramine data at
500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2>NBI-1>NBI-3>diphenhydramine >NBI4,
whereas the rank order for clearance was
NBI-4>diphenhydramine>NBI-1>NBI-3 >NBI-2.
Human microdosing provided estimates of clinical pharmacokinetics of four structurally-related compounds, which were deemed useful for
compound selection. |
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