Wilson A M, Clark D J, McFarlane L, Lipworth B J
Department of Clinical Pharmacology, Ninewells Hospital & Medical School, University of Dundee, Scotland, UK.
Eur J Clin Pharmacol. 1997;53(1):33-7. doi: 10.1007/s002280050333.
This study was conducted to compare the adrenal suppression of inhaled fluticasone propionate and triamcinolone acetonide in healthy volunteers, both given via their respective pressurised metered dose inhaler (pMDI) devices at high doses within the manufacturers recommended dose range.
We used a single (investigator) blind, randomised, crossover design comparing a total daily dose of 1.625 mg fluticasone propionate delivered via a pMDI, 1.60 mg daily of triamcinolone acetonide delivered via a pMDI with integrated spacer, or placebo pMDI; each drug was given in two divided doses at 0800 hours and 2200 hours over a 24-h period. Each drug treatment was separated by a 1-week washout.
Twelve normal subjects mean age 27.5 years were studied.
Blood samples were taken for 0800 hours plasma cortisol, i.e. 10 h following the second dose. Ten hour urine collections (2200 hours until 0800 hours) were taken for urinary cortisol and creatinine excretion.
For the 0800 hours plasma cortisol (geometric mean, nmol.1(-1) compared with placebo (353) fluticasone propionate (138) produced significant (P < 0.05) suppression (2.57-fold difference), whereas triamcinolone acetonide (263) did not (1.34-fold difference). Fluticasone propionate produced a 1.91-fold greater adrenal suppression than triamcinolone acetonide (95% CI 1.10 to 3.33). Individual subjects with abnormally low 0800 hours cortisol values < 150 nmol.1(-1) (< 5.4 micrograms/dl) were n = 4 for fluticasone propionate and n = 0 for triamcinolone acetonide. Overnight urinary cortisol/creatinine ratio (geometric mean, nmol/mmol) did not show any difference between fluticasone propionate (1.48) and triamcinolone acetonide (1.60), with both producing significant suppression versus placebo (4.01): triamcinolone acetonide 2.50-fold difference (95% CI 1.45-4.24); fluticasone propionate 2.71-fold difference (95% CI 1.57-4.69).
Fluticasone propionate 1.625 mg/day (pMDI) produced an approximately two-fold greater adrenal suppression of 0800 hours plasma cortisol than triamcinolone acetonide 1.60 mg per day (Oral Inhaler) when given twice daily, and one third of subjects with fluticasone had abnormally low 0800 hours cortisol values < 150 nmol.1(-1) (< 5.4 micrograms.dl-1. There were no differences between the drugs for urinary cortisol excretion. Further dose-ranging studies are required at steady-state in asthmatic subjects in order to see whether differences occur at lower doses on the steep part of the dose-response curve for both plasma and urinary cortisol suppression.
本研究旨在比较健康志愿者吸入丙酸氟替卡松和曲安奈德后肾上腺抑制情况，二者均通过各自的压力定量吸入器（pMDI）装置，在制造商推荐剂量范围内给予高剂量。
我们采用单（研究者）盲、随机、交叉设计，比较通过pMDI每日总剂量给予1.625mg丙酸氟替卡松、通过带有一体化储雾罐的pMDI每日给予1.60mg曲安奈德或安慰剂pMDI；每种药物在24小时内于08:00和22:00分两次给药。每种药物治疗之间间隔1周洗脱期。
研究了12名平均年龄27.5岁的正常受试者。
于08:00采集血样检测血浆皮质醇，即第二次给药后10小时。收集10小时尿液（22:00至08:00）检测尿皮质醇和肌酐排泄。
对于08:00的血浆皮质醇（几何均值，nmol·L⁻¹），与安慰剂（353）相比，丙酸氟替卡松（138）产生了显著（P<0.05）抑制（差异2.57倍），而曲安奈德（263）未产生（差异1.34倍）。丙酸氟替卡松产生的肾上腺抑制比曲安奈德大1.91倍（95%CI 1.10至3.33）。08:00皮质醇值异常低<150nmol·L⁻¹（<5.4μg/dl）的个体，丙酸氟替卡松组为n = 4，曲安奈德组为n = 0。过夜尿皮质醇/肌酐比值（几何均值，nmol/mmol）在丙酸氟替卡松（1.48）和曲安奈德（1.60）之间未显示出任何差异，二者与安慰剂相比均产生显著抑制（4.01）：曲安奈德差异2.50倍（95%CI 1.45 - 4.24）；丙酸氟替卡松差异2.71倍（95%CI 1.57 - 4.69）。
每日1.625mg（pMDI）丙酸氟替卡松在每日两次给药时，对08:00血浆皮质醇的肾上腺抑制作用比每日1.60mg曲安奈德（经口腔吸入器）大近两倍，且三分之一使用丙酸氟替卡松的受试者08:00皮质醇值异常低<150nmol·L⁻¹（<5.4μg·dl⁻¹）。两种药物在尿皮质醇排泄方面无差异。需要在哮喘患者稳态下进行进一步的剂量范围研究，以观察在血浆和尿皮质醇抑制的剂量 - 反应曲线陡峭部分较低剂量时是否存在差异。
