biodistribution

Biodistribution is the study of the spatial and temporal distribution of a substance within a living organism following administration. It maps which tissues and organs accumulate the substance, at what levels, and for how long. Biodistribution is a key component of pharmacokinetics and informs exposure, efficacy, and safety, complementing absorption, metabolism, and excretion (ADME).

Determinants include the physicochemical properties of the substance (molecular size, polarity, lipophilicity, charge), formulation, route of administration, plasma protein binding, and metabolic stability. Biological barriers such as the blood‑brain barrier, tissue perfusion, and organ-specific uptake mechanisms influence distribution. Disease states can alter perfusion, receptor expression, and clearance, shifting biodistribution.

Common methods to measure biodistribution include in vivo imaging with PET or SPECT using radiolabeled compounds, fluorescence imaging for larger preclinical models, and ex vivo techniques such as gamma counting, autoradiography, and LC-MS/MS analysis of tissue samples. Preclinical studies often report tissue concentrations over time to derive pharmacokinetic parameters and tissue residence times.

Applications span drug development, radiopharmaceuticals, and delivery systems such as nanoparticles or antibody-drug conjugates. Typical patterns include high liver and spleen uptake for nanoparticulate formulations, rapid renal excretion for small hydrophilic molecules, and restricted brain distribution unless active transport or barrier disruption is involved. Biodistribution data support dose selection, safety assessment, and translation from animal models to humans.

Limitations include species differences, reproducibility of tissue sampling, and the challenge of correlating tissue levels with pharmacodynamic effects. Regulatory considerations involve dosimetry for radiopharmaceuticals and rigorous reporting of distribution data.