TI (TD50 / ED50 in clinic; LD50 / ED50 in animal toxicology)
units
Dimensionless dose or exposure ratio
equation
TI = TD50 / ED50 (clinical) or TI = LD50 / ED50 (preclinical animal studies)
pioneer
Paul Ehrlich (chemotherapeutic index concept) and quantitative dose-response toxicology
Core Principles & Analysis
In clinical pharmacology, the therapeutic index is defined as the ratio of the median toxic dose (TD50, causing an unacceptable adverse effect in 50% of patients) to the median effective dose (ED50), whereas preclinical animal studies traditionally used LD50 / ED50.
Drugs with a narrow therapeutic index (such as digoxin, lithium, warfarin, phenytoin, and colchicine, where TI can be 2 to 3) require therapeutic drug monitoring (TDM) and careful CYP450/transporter interaction management to avoid life-threatening overdose or sub-therapeutic failure.
Because TD50 and ED50 curves may have different slopes, modern regulatory safety margins also evaluate the Certain Safety Factor (TD1 / ED99) and the pharmacokinetic exposure margin comparing human Cmax/AUC at the therapeutic dose to the preclinical No-Observed-Adverse-Effect Level (NOAEL).