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

A scientist wearing a blue glove uses tweezers to handle a small component on a metallic Carbon-14 Microtracer cathode with hexagonal screws.

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 scientist uses a pipette to prepare samples for Phase 0 microdosing studies, focusing on early pharmacokinetics in a controlled laboratory setting.

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)