Active eosinophilic esophagitis is associated with impaired elimination of budesonide by cytochrome P450 3A enzymes.
OBJECTIVE
Topically administered glucocorticoids such as budesonide have the potential of being established as first-line medical treatment of eosinophilic esophagitis (EoE). Safety of budesonide is based on high elimination by cytochrome P450 3A (CYP3A) enzymes. We aimed to investigate systemic absorption and elimination of a new budesonide formulation in patients with active EoE in comparison with healthy controls.


METHODS
After single and multiple doses of orodispersible budesonide (4 mg/day) the parent drug, its CYP3A-dependent metabolites, and endogenous cortisol were determined in 12 adult patients with active EoE and 12 healthy controls. An approved ileal-release formulation of budesonide was taken for reference. Molar ratios of metabolite formation in plasma were used as indices of CYP3A metabolic function.


RESULTS
CYP3A-dependent metabolite formation was significantly reduced in patients with active EoE as compared to healthy controls. Impaired biotransformation was reflected by a significantly higher extent of budesonide absorption and elongated elimination half-life in EoE patients. Comparison of morning serum cortisol levels at baseline with those after 1 week of treatment with budesonide revealed a significant decrease in EoE patients but not in healthy subjects.


CONCLUSIONS
Active EoE is associated with reduced elimination of budesonide via CYP3A, the major subfamily of drug-metabolizing enzymes in humans.
Dr. Falk Pharma GmbH, Freiburg, Germany. dilger@drfalkpharma.de
Karin
K
Dilger
Luis
L
Lopez-Lazaro
Claudia
C
Marx
Christian
C
Bussmann
Alex
A
Straumann
D000287:Administration, Topical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001711:Biotransformation; D019819:Budesonide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D057765:Eosinophilic Esophagitis / Q000188:drug therapy*; D005260:Female; D005938:Glucocorticoids / Q000493:pharmacokinetics*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged
D005938:Glucocorticoids; D019819:Budesonide; D051544:Cytochrome P-450 CYP3A; D006854:Hydrocortisone