Therapeutic Index & Measures of Drug Safety

Introduction

• Therapeutic index (TI) — 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.
• 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 curve that describes the magnitude of effect in one individual or tissue.
• 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.
• Cross-link — the graded dose–response curve, potency, efficacy, EC₅₀/ED₅₀ and E_max that underpin these safety measures are developed under receptor-pharmacodynamics; this topic takes those primitives and extends them to the population/quantal level.
• 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 the likelihood of efficacy is high while the probability of toxicity stays low.