2. Mechanisms of Action

bioavailability

Definition

Bioavailability is the fraction of an administered drug dose that reaches systemic circulation in its active form, typically expressed as a percentage. It represents a critical pharmacokinetic parameter that determines drug efficacy and dosing requirements. Bioavailability is influenced by multiple factors including absorption rate, first-pass metabolism in the liver and gut, drug formulation, and physicochemical properties like solubility and permeability. For intravenous administration, bioavailability is 100% by definition, while oral routes often exhibit reduced bioavailability due to incomplete absorption and pre-systemic metabolism. Understanding bioavailability is essential for rational drug design, dose optimization, and predicting drug-drug interactions that may alter systemic exposure and therapeutic outcomes.

Visualize bioavailability in Nodes Bio

Researchers can map bioavailability-modifying factors as network nodes, connecting drug molecules to metabolizing enzymes (CYP450s), transporters (P-glycoprotein, OATP), and absorption barriers. Network visualization reveals how genetic variants, co-administered drugs, or disease states create cascading effects on drug exposure, enabling identification of critical control points that influence therapeutic efficacy and safety profiles across patient populations.

Visualization Ideas:

  • Drug-metabolizing enzyme interaction networks showing CYP450 family members and their substrate relationships
  • Transporter-drug networks mapping ABC and SLC transporters affecting intestinal absorption and hepatic uptake
  • Multi-layer networks connecting drug formulations to absorption barriers, metabolic pathways, and genetic variants influencing bioavailability
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Example Use Case

A pharmaceutical team developing an oral kinase inhibitor discovers poor bioavailability (12%) in Phase I trials. Using network analysis, they map the compound's interactions with intestinal CYP3A4, efflux transporters, and food components. The visualization reveals that grapefruit juice components strongly inhibit CYP3A4, increasing bioavailability to 45%. This network insight guides formulation strategies and identifies patient subgroups with CYP3A4 polymorphisms who may require dose adjustments to maintain therapeutic drug levels.

Related Terms

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