Premium
Flunisolide metabolism and dynamics of a metabolite
Author(s) -
Chaplin Melvin D,
Rooks Wendell,
Swenson Edward W,
Cooper William C,
Nerenberg Clinton,
Chu Nancy I
Publication year - 1980
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1980.54
Subject(s) - metabolite , chemistry , pharmacology , pharmacokinetics , active metabolite , metabolism , medicine , endocrinology
Flunisolide (6α‐fluoro‐11β,16α,17α,21‐tetrahydroxypregna‐1,4‐diene‐3,20‐dione 16,17‐acetonide) is a potent corticoid used clinically in topical formulations. Three men were given single 2‐mg intravenous and oral doses of 14 C‐labeled flunisolide and plasma and urine concentrations of flunisolide and a major metabolite, 6β,11β,16α,17α,21 ‐penta‐hydroxypregna‐1,4‐diene‐3,20‐dione 16,17‐acetonide (6β‐OH metabolite) were determined. Oral flunisolide was metabolized rapidly and extensively to the 6β‐OH metabolite and to conjugates; comparison in the intravenous dose kinetics suggested significant first‐pass metabolism. In a separate study in 12 normal subjects, flunisolide in plasma was quantitated by radioimmunoassay (RIA); average systemic availability was 20%. The apparent volume of distribution (Vdβ) of flunisolide was large and systemic clearance and apparent oral clearance values were high. The 6β‐OH metabolite had corticoid activities no more than 3 times that of hydrocortisone in rats as measured by thymolytic, anti‐inflammatory, and adrenal‐suppressive assays, whereas flunisolide had 180 to 550 times the activity of hydrocortisone. These data offer a metabolic explanation for the clinical observation that flunisolide can be administered intranasally and by inhalation in therapeutically effective doses without causing significant reduction in adrenal function. Clinical Pharmacology and Therapeutics (1980) 27, 402–413; doi: 10.1038/clpt.1980.54