Affrime M B, Kosoglou T, Thonoor C M, Flannery B E, Herron J M
Schering-Plough Research Institute, Kenilworth, NJ 07033-0539, USA.
Chest. 2000 Dec;118(6):1538-46. doi: 10.1378/chest.118.6.1538.
To investigate the potential for mometasone furoate (MF) to exert systemic effects following administration by dry powder inhaler (DPI) or metered-dose inhaler (MDI).
Three randomized, evaluator-blind, placebo-controlled, parallel-group, 28-day studies.
Adults with mild-to-moderate persistent asthma.
Study 1 (12 patients per treatment group; MF DPI at 200 microg bid, 400 microg qd, 800 microg qd, or 1,200 microg qd). Study 2 (16 patients per treatment group; MF DPI at 400 microg bid or 800 microg bid, or oral prednisone at 10 mg qd). Study 3 (16 patients per treatment group; MF MDI at 400 microg bid or 800 microg bid, or fluticasone propionate [FP] at 880 microg bid by MDI).
Study 1. Plasma concentrations were near the lower limit of quantitation (50 pg/mL) at the MF DPI 400-microg qd dosage and approximately 250 pg/mL at the 1,200-microg qd dosage. The area under the curve for serum cortisol concentrations over 24 h (AUC(24)) was essentially unaltered at all doses. Study 2. Plasma levels over days 7 to 28 were 100.3 +/- 5.9 pg/mL (mean +/- SEM) for MF DPI 400 microg bid, and 181.0 +/- 10.9 pg/mL for 800 microg bid. Although there were relatively low levels of suppression (19 to 25%) at earlier time points for MF DPI 400 microg bid, serum cortisol AUC(24) levels at day 28 were similar to placebo. MF DPI 800 microg bid and oral prednisone both decreased serum cortisol AUC(24) levels at days 7 to 28 by 28.0 +/- 8.3% and 67.2 +/- 3.6%, respectively. The response to cosyntropin was normal in 15, 14, 11, and 1 of the patients in the placebo, MF DPI 400 microg bid, MF DPI 800 microg bid, and prednisone groups, respectively. Study 3. MF MDI caused even less systemic exposure than by DPI. MF MDI 800 microg bid (24.0 +/- 3.1%) and FP (51.7 +/- 3.8%) caused a significant decrease in serum cortisol AUC(24) on days 14 to 28. MF MDI 400 microg bid was similar to placebo treatment at all time points.
The MF 800-microg bid dosage (1,600 microg/d), which is twice the highest projected clinical dosage, represents the lower limit for consistently detectable systemic effects of MF.
探讨糠酸莫米松（MF）通过干粉吸入器（DPI）或定量吸入器（MDI）给药后产生全身效应的可能性。
三项随机、评估者盲法、安慰剂对照、平行组、为期28天的研究。
轻至中度持续性哮喘的成年人。
研究1（每个治疗组12名患者；MF DPI，剂量分别为200μg，每日两次；400μg，每日一次；800μg，每日一次；或1200μg，每日一次）。研究2（每个治疗组16名患者；MF DPI，剂量为400μg，每日两次或800μg，每日两次；或口服泼尼松，剂量为10mg，每日一次）。研究3（每个治疗组16名患者；MF MDI，剂量为400μg，每日两次或800μg，每日两次；或氟替卡松丙酸酯[FP]，通过MDI给药，剂量为880μg，每日两次）。
研究1。在MF DPI剂量为400μg，每日一次时，血浆浓度接近定量下限（50pg/mL），在剂量为1200μg，每日一次时约为250pg/mL。所有剂量下，24小时血清皮质醇浓度曲线下面积（AUC(24)）基本未改变。研究2。在第7至28天，MF DPI剂量为400μg，每日两次时血浆水平为100.3±5.9pg/mL（均值±标准误），800μg，每日两次时为181.0±10.9pg/mL。尽管在早期时间点，MF DPI剂量为400μg，每日两次时抑制水平相对较低（19%至25%），但在第28天血清皮质醇AUC(24)水平与安慰剂相似。MF DPI剂量为800μg，每日两次和口服泼尼松在第7至28天分别使血清皮质醇AUC(24)水平降低28.0±8.3%和67.2±3.6%。在安慰剂组、MF DPI剂量为400μg，每日两次组、MF DPI剂量为800μg，每日两次组和泼尼松组中，分别有15名、14名、11名和1名患者对促肾上腺皮质激素的反应正常。研究3。MF MDI引起的全身暴露甚至比DPI更少。MF MDI剂量为800μg，每日两次（24.0±3.1%）和FP（51.7±3.8%）在第14至28天使血清皮质醇AUC(24)显著降低。MF MDI剂量为400μg，每日两次在所有时间点均与安慰剂治疗相似。
MF剂量为800μg，每日两次（1600μg/天），是预计最高临床剂量的两倍，代表了MF持续可检测到全身效应的下限。
