Pulmonary disposition of the potent glucocorticoid budesonide, evaluated in an isolated perfused rat lung model.
Budesonide is a potent glucocorticoid developed for the local treatment of respiratory disorders such as bronchial asthma and allergic rhinitis. We now report the lung disposition of 3H-budesonide administered either via the air passages or via the pulmonary circulation using isolated perfused and ventilated rat lungs. A rapid initial absorption was found after intratracheal administration of a clinically relevant dose of the drug. However, about half of the given dose was slowly released into the lung perfusate. The lung uptake of budesonide from the pulmonary circulation was relatively high (lung extraction ratio about 0.12). These data points to a high lung affinity for budesonide. The drug was not biotransformed in the lung. The high lung affinity and absence of lung metabolism can be important factors to explain the good therapeutic effects seen with budesonide in the clinic.
Ryrfeldt
A
A
AB Astra, Safety Assessment, Södertälje, Sweden.
Persson
G
G
Nilsson
E
E
D000818:Animals; D019819:Budesonide; D005938:Glucocorticoids / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D011282:Pregnenediones / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains
D005938:Glucocorticoids; D011282:Pregnenediones; D019819:Budesonide