Phase 0 Microdosing Services

Pharmaron offers the design and execution of Phase 0 microdosing studies to help enable our partners confidently select the most promising lead candidate for further, continued drug development. Sub-pharmacological human microdosing studies (Phase 0) can provide accurate, predictive human PK/ADME data (compared to allometry) for many new compounds.

Scalability of PK data for microdosing studies is linear for approximately 85% of drugs that are orally administered and 100% for drugs administered IV. The best model of human is human, especially when metabolism data from a variety of animal models is not providing a predictive or accurate model for human. This data can de-risk lead candidate selection for successful Phase I clinical development. Microdosing can also address absorption and systemic exposure, in addition to assessing exposure in specific tissues such as skin and lung.

For Phase 0 clinical designs, the microdose can be administered by both the oral and IV routes in an oral/IV cross-over design. This design provides data for both metabolism and PK, as well as absolute bioavailability.

Capabilities

Carbon-14 Microtracers

Ultra-sensitive AMS

Accelerated Carbon-14 Clinical Programs

Phase 0 Microdosing

Absolute Bioavailability and IV Pharmacokinetics

Mass Balance by AMS

Metabolite Profiling Using AMS

AMS for Carbon-14 Non-clinical Studies

Carbon-14 Radiolabels and AMS for Biologics

Microdosing Studies with either Stable (¹³C) or Radiolabelled Isotopes (¹⁴C) of Carbon

Microdose administration of stable label (¹³C drug) with quantitation by LC-MS/MS (assuming sensitivity of the assay can reach the required LLOQ)
Microdose administration of radiolabel (¹⁴C drug) with quantitation by LC+AMS (ultra sensitivity of AMS typically reaches much lower LLOQs than LC-MS/MS with more rapid method development and validation turn-around times)

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A researcher wearing a white lab coat and purple gloves uses a pipette in a laboratory. She has protective eyewear and is focused on her bioanalytical development work, with lab equipment and supplies visible in the background.

Microdosing Applications

Lead and backup compound selection
Comparator studies with existing marketed drug(s)
Drug-drug interaction (DDI) studies using cassette microdosing with probe substrates (for enzyme inhibition/induction)
Combination ¹⁴C microdose – ¹¹C PET PK/PD studies, for CNS compounds
Drug targeting and tissue disposition (e.g. anti-cancer drugs in DNA samples from human tumor biopsies, respiratory drugs in bronchoalveolar lavage samples for human lung disposition)