Therapeutic Index |

Therapeutic Index

Inhaled corticosteroid therapy in children demands the optimal therapeutic index, as defined by the ratio between efficacy and systemic bioavailability.


Only the dose deposited in the lower airways contribute to the efficacy. The importance of the exact location of the deposition is unknown though it has been speculated that peripheral deposition may be advantageous since this is the main location of the disease process. Differences in aerosol particle distribution may greatly change the deposition pattern within the lung presumably with a corresponding change in efficacy.

Systemic Bioavailability

Lung dose: Inhaled corticosteroids (ICS) are not metabolized in the lungs and need to pass through the blood to be metabolized in the lungs. Therefore any ICS deposited in the lung is eventually systemically active.

Importantly, devices delivering a high lung dose therefore lead to equally high systemic exposure (Ref 4).

Oral dose: the inhaled dose that does not reach the lung passes to the gut where is may be absorbed and passes through the liver to the systemic circulation. The absorption and first-pass elimination in the liver differs among steroids and the oral contribution to the systemic activity is often minimal compared to the contribution of the lung dose.
Professor Hans Bisgaard • Copenhagen • Denmark •