Expressed as TI = TD50 / ED50, the therapeutic index compares the median toxic dose (TD50) , the dose causing toxicity in 50% of a study population , against the median effective dose (ED50). A high TI indicates a relatively wide margin between an effective dose and a harmful one; a low TI indicates that effective and toxic doses are close together, requiring careful dosing management.
In clinical and regulatory contexts, the related concept of the therapeutic window (or therapeutic range) describes the plasma concentration range within which a substance is considered to produce its pharmacological effect without unacceptable adverse outcomes. Substances with a narrow therapeutic index are subject to heightened regulatory scrutiny and, in Australia, may attract specific scheduling conditions under the Poisons Standard (the current iteration of which is maintained by the Therapeutic Goods Administration under the Therapeutic Goods Act 1989).
The concept has direct relevance to how the TGA evaluates risk-benefit profiles during the registration and scheduling of medicines. Substances classified as Schedule 4 (prescription only) or Schedule 8 (controlled drug) under the Poisons Standard frequently carry narrow therapeutic index considerations as part of the rationale for restricted access.
The therapeutic index originates in classical pharmacology and was formalised in the early twentieth century. It remains a foundational metric in drug development, regulatory toxicology, and clinical pharmacy education, though its limitations , including inter-individual variation in metabolism, age, body composition, and co-administration of other substances; are well recognised in contemporary pharmacokinetic literature.
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