Chu N I, Amos B A, Tökés L, Maddox M L, Matin S B, Hama K M, Patterson J W, Wagner P J, Bell J P, Chaplin M D
Drug Metab Dispos. 1979 Mar-Apr;7(2):81-9.
Flunisolide (6 alpha-fluoro-11 beta, 16 alpha, 17 alpha, 21-tetrahydroxypregna-1,4-diene-3,20-dione 16,17-acetonide) administered as a single iv or oral dose to rats, mice, dogs, rhesus monkeys, and cynomolgus monkeys had a plasma t 1/2 of 1-3.5 hr and was eliminated mainly via the bile. After iv administration of 14C-labeled flunisolide, radioactivity was widely distributed into tissues and organs. The apparent volume of distribution of flunisolide in these five species was 3.0-8.0 liters/kg. A major metabolite isolated from rhesus monkey urine was shown to be 6 beta, 11 beta, 16 alpha, 17 alpha, 21-pentahydroxypregna-1,4-diene-3,20-dione 16,17-acetonide (6 beta-OH metabolite). Free 6 beta-OH metabolite was a major radioactive entity detected in urine of all species given radiolabeled flunisolide, whereas flunisolide conjugated with glucuronic acid and/or sulfate was a major metabolite detected in the bile of rats, dogs, and cynomolgus monkeys. Following the oral administration of radiolabeled flunisolide, radioactivity was rapidly and efficiently absorbed in all species, but in the rhesus and cynomolgus monkeys most of the plasma radioactivity was due to the 6 beta-OH metabolite and to water-soluble conjugates, suggesting extensive first-pass metabolism of flunisolide.
将氟尼缩松（6α-氟-11β,16α,17α,21-四羟基孕甾-1,4-二烯-3,20-二酮16,17-缩丙酮）以单次静脉注射或口服剂量给予大鼠、小鼠、狗、恒河猴和食蟹猴后，其血浆半衰期为1 - 3.5小时，主要通过胆汁消除。静脉注射14C标记的氟尼缩松后，放射性广泛分布于组织和器官中。氟尼缩松在这五个物种中的表观分布容积为3.0 - 8.0升/千克。从恒河猴尿液中分离出的一种主要代谢产物被证明是6β,11β,16α,17α,21-五羟基孕甾-1,4-二烯-3,20-二酮16,17-缩丙酮（6β-OH代谢产物）。游离的6β-OH代谢产物是所有给予放射性标记氟尼缩松的物种尿液中检测到的主要放射性物质，而与葡萄糖醛酸和/或硫酸盐结合的氟尼缩松是大鼠、狗和食蟹猴胆汁中检测到的主要代谢产物。口服放射性标记的氟尼缩松后，所有物种均能快速有效地吸收放射性，但在恒河猴和食蟹猴中，大部分血浆放射性归因于6β-OH代谢产物和水溶性结合物，这表明氟尼缩松存在广泛的首过代谢。
