Therapeutic index

The therapeutic index (TI) is a measure of the safety of a drug. It indicates the ratio of the lethal dose of a drug in relation to the effective dose and is calculated from the quotient: LD5: lethal dose at which 5% of individuals die/ ED95: single dose at which 95% of the maximum effect is achieved or the desired effect occurs in 95% of individuals. The formula is therefore: LD5/ ED95 (Smith LS et al. 2018).

The higher the LD5/ED95 ratio, the safer a drug is to use. The therapeutic index can also be interpreted reliably if the dose-response curve and the dose-lethality curve do not show an approximately parallel course. The therapeutic index is therefore more reliable than the therapeutic range.

In dermatological therapy with external glucocorticoids, for example, the therapeutic index plays a role insofar as only those preparations with a favorable side effect profile should be used for prolonged application. The molecular structural features that increase the binding affinity and selectivity of the glucocorticoid receptor are responsible for the topical anti-inflammatory effect. Consequently, efficacy and therapeutic index can be correlated (Daley-Yates PT 2015). Thus, very potent class IV glucocorticoids (according to Niedner) for chronic inflammatory dermatoses are only used in a restricted, localized manner and only in special localizations (not intertriginous). The correct application quantity can be estimated with the help of the so-called fingertip unit.

1. Daley-Yates PT (2015) Inhaled corticosteroids: potency, dose equivalence and therapeutic index. Br J Clin Pharmacol 80:372-380.
2. Smith LS et al (2018) The Therapeutic Index. Pediatr Crit Care Med 19:775-776.