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Review
, 10 (5), 337-350

Intra-Target Microdosing (ITM): A Novel Drug Development Approach Aimed at Enabling Safer and Earlier Translation of Biological Insights Into Human Testing

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Review

Intra-Target Microdosing (ITM): A Novel Drug Development Approach Aimed at Enabling Safer and Earlier Translation of Biological Insights Into Human Testing

T Burt et al. Clin Transl Sci.

Figures

Figure 1
Figure 1
Intra‐target microdosing (ITM) in drug development. ITM may result in 8–12‐month quicker arrival at human‐based “go‐no‐go” decisions. The figure illustrates the traditional (black) and ITM (red) pathways for entry into human testing: IND (Investigational New Drug) or Exploratory IND (eIND), respectively. GMP, Good Manufacturing Practices; PK, pharmacokinetics; PD, pharmacodynamics.
Figure 2
Figure 2
Intra‐target microdosing (ITM): Schematic of input and output. By generating concentrations higher than the pharmacodynamic (PD) threshold, ITM allows the capture of local PD data relevant to full (pharmacological, therapeutic‐level) exposure, in addition to systemic PK data. Multiple infusion profiles are possible depending on desired exposure–response profiles.
Figure 3
Figure 3
PKPD continuum. ITM allows study of drug effects in the following domains: (I) plasma PK; (II) target/tissue PK (for efficacy and toxicity targets); (III) receptor binding and displacement; (IV) pharmacological effects; biomarkers and/or clinical outcomes. PD, pharmacodynamics; PK, pharmacokinetics; Cu, concentration unbound in tissue; O, clinical outcome; BM, biomarkers/metabolites; SEP, surrogate end points. (Adapted from Burt et al. 2016).

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References

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