pulmicort and Ear-Diseases

Budesonide (Bud) is a nonhalogenated glucocorticoid with high anti-inflammatory potency and low systemic side effects. However, the poor water solubility of Bud affects its dissolution and release behavior, thus influencing its anti-inflammatory effect. This study was aimed at synthesizing and evaluating novel conjugates of Bud, hoping to increase the anti-inflammatory activity of Bud by improving its water solubility.. Seven novel Bud conjugates (. As compared to Bud, the equilibrium solubility of. The amino acid ester compounds budesonide-21-glycine ester (

Topics: A549 Cells; Animals; Anti-Inflammatory Agents, Non-Steroidal; Budesonide; Cell Survival; Ear Diseases; Edema; Humans; Interleukin-6; Male; Mice; Mice, Inbred Strains; Molecular Structure; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Xylenes

The use of topical glucocorticosteroid therapy on large skin areas or in the lung is sometimes restricted by the occurrence of unwanted, general corticoid actions owing to a profound systemic absorption. To decrease this risk potent glucocorticoids with an enhanced ratio between their topical and their systemic glucocorticoid potencies are wanted. Therefore, structure-activity studies were performed in rat models to investigate what influences the type of substitution in the 16 alpha, 17 alpha-acetal group and the introduction of fluorine in the 9 alpha- or the 6 alpha, 9 alpha-positions have on the topical and the systemic activities, respectively. The introduction of an unsymmetrical 16 alpha, 17 alpha-acetal group (named acetal type B) markedly enhanced the topical anti-inflammatory potency compared with that of the conventional 16 alpha, 17 alpha-acetonide group (named acetal type A). Both acetal types had a similar systemic glucocorticoid potency, however, 9 alpha-Fluoro and especially 6 alpha, 9 alpha-difluoro substitution, on the other hand, enhanced the systemic glucocorticoid activity more than they raised the topical anti-inflammatory potency. Optimal topical to systemic activity ratio was obtained with a nonhalogenated corticoid of acetal type B structure. This compound, budesonide, had at least the same high topical anti-inflammatory potency as fluocinolone acetonide but was about 10 times less potent than this reference to induce systemic glucocorticoid actions. Its lower systemic activity is probably due to a more rapid biotransformation in the liver.

Topics: Acetals; Administration, Topical; Animals; Anti-Inflammatory Agents; Budesonide; Ear Diseases; Edema; Fluorine; Glucocorticoids; Humans; Male; Organ Size; Pregnenediones; Rats; Rats, Inbred Strains; Skin; Structure-Activity Relationship; Thymus Gland