Mometasone furoate degradation and metabolism in human biological fluids and tissues

• Published in: Biopharmaceutics & drug disposition 2003-11, Vol.24 (8), p.321-333
• Main Authors: Teng, Xiao Wei, Cutler, David J., Davies, Neal M.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Biotransformation; Bones, joints and connective tissue. Antiinflammatory agents; degradation; Female; glucocorticoid; Humans; In Vitro Techniques; Intestines - metabolism; Lung - metabolism; Male; Medical sciences; metabolism; Microsomes, Liver - metabolism; Middle Aged; Models, Biological; mometasone; Mometasone Furoate; Pharmacology. Drug treatments; Plasma - chemistry; Pregnadienediols - blood; Pregnadienediols - pharmacokinetics; Pregnadienediols - urine; Urine - chemistry
• ISSN: 0142-2782; 1099-081X
• DOI: 10.1002/bdd.362

The in vitro metabolic and non‐metabolic degradation kinetics of mometasone furoate (MF) was investigated in selected human biological fluids and subcellular fractions of tissues. Qualitative and quantitative differences in transformation profiles of MF were observed among human biological media. Degradation was the major event in plasma and urine with four new degradation products identified; A: 21‐chloro‐17α‐hydroxy‐16α‐methyl‐9β,11β‐oxidopregna‐1,4‐diene‐3,20‐dione 17‐(2‐furoate), B: 9α,21β‐dichloro‐11β,21α‐dihydroxy‐16α‐methylpregna‐1,4,17,20‐tetraen‐3‐one 21‐(2‐furoate), C: 21β‐chloro‐21α‐hydroxy‐16α‐methyl‐9β,11β‐oxidopregna‐1,4,17,20‐tetraen‐3‐one 21‐(2‐furoate), and D: 21‐chloro‐17α‐hydroxy‐16α‐methyl‐9β,11β‐oxidopregna‐1,4‐diene‐3,20‐dione. A, B and C were predominant and D was minor in plasma while A and C were predominant in urine. Hydrolysis of the 17‐ester bond of MF was not a major event in plasma. The turnover of MF in plasma was faster than that in phosphate buffers of pH 7.4. Metabolism of MF occurred primarily and rapidly in liver, appreciably in intestine, but negligibly in in vitro lung tissue. While 6β‐hydroxylation was a major metabolic pathway for MF in microsomes of both human liver and intestine, other parallel and subsequent metabolism pathways could also be involved. If these degradation and metabolic products are also formed and active in humans in vivo, both MF and its ‘active’ products need to be taken into account when determining the systemic bioavailability of MF and in establishing concentration‐effect relationships with this drug. Copyright © 2003 John Wiley & Sons, Ltd.