Therapeutic Index & Measures of Drug Safety

Therapeutic Index & Measures of Drug Safety

1. Definition & scope

• Therapeutic index (TI) is a quantitative expression of drug safety — the ratio of the dose (or concentration) producing toxicity to the dose producing the desired therapeutic effect; it reflects how selective a drug is in producing its desired effects relative to its toxicity/lethality (G&G 14e Ch.3, pp.53–4).
• This topic sits within population (quantal) pharmacodynamics — it answers "in what fraction of a population does a given dose work, and in what fraction does it harm?", as distinct from the graded (continuous) concentration–response curve that describes the magnitude of effect in a single individual or tissue (G&G 14e Ch.3, pp.51–4).
• The gap between the dose–response curve (DRC) for the therapeutic effect and the DRC for the adverse/toxic effect defines the safety margin (also termed the therapeutic index) of a drug — the wider this separation, the safer the drug (KDT 8e Ch.4, p.65).
• Cross-link: the graded dose–response curve, potency, efficacy, EC₅₀/ED₅₀ and E_max that underpin these safety measures are developed in detail under receptor-pharmacodynamics — this topic uses those primitives and extends them to the population/quantal level (R&D Ch.2, pp.16–17; G&G 14e Ch.3, pp.51–2).
• Clinical purpose: TI and its derivatives let the prescriber and the regulator rank drugs by inherent safety, identify which drugs need plasma-level monitoring (TDM), and set dosing so that the likelihood of efficacy is high while the probability of toxicity stays low (G&G 14e Ch.3, p.54; KDT 8e Ch.4, p.65).