ADME — Absorption, Distribution, Metabolism, and Excretion — is
essential for predicting how a drug behaves in the body. These processes
determine whether a compound reaches its target at the right concentration, for
the right duration, and without causing harm. In drug discovery, ADME studies
guide compound optimization, reduce late‑stage failures, and support rational
design of safer, more effective therapeutics.
Drug discovery investigate metabolism and pharmacokinetics using a combination of in vitro assays, in vivo studies, and in silico modeling. Each component answers a different question about how a drug behaves in the body.
| Pharmacokinetics | Study Methods |
|---|---|
| Absorption | Caco‑2 permeability assays Simulate intestinal absorption using human epithelial cells PAMPA (Parallel Artificial Membrane Permeability Assay) Measures passive diffusion across a lipid membrane Solubility and dissolution testing Determines whether the compound can dissolve in GI fluids Transporter assays Identify efflux or uptake interactions (P‑gp, BCRP, OATP) |
| Distribution | Plasma protein binding assays (e.g., equilibrium dialysis) Measures free vs bound drug. Tissue distribution studies (in vivo) Quantify drug levels in organs after dosing. Blood–brain barrier models For CNS drugs, using MDCK‑MDR1 or primary cell models. Volume of distribution (Vd) calculations Derived from PK studies. |
| Metabolism | Liver microsome assays Measure metabolic stability and intrinsic clearance. Hepatocyte assays Capture both phase I and phase II metabolism. CYP450 inhibition/induction panels Identify DDI risks early. Metabolite identification (LC‑MS/MS, NMR) Characterize metabolic pathways. Recombinant enzyme assays Pinpoint which CYP isoforms are involved. |
| Excretion | In vivo clearance studies Measure renal and hepatic elimination. Bile duct–cannulated animal models Quantify biliary excretion. Transporter assays (OAT, OCT, MATE) Predict renal secretion. Mass balance studies Track total recovery of drug + metabolites. |