Brazier David, Perry Robert, Keane Jim, Barrett Katie, Elmaleh David R
AZTherapies, Inc, 222 Berkeley Street, 12th Floor, Boston, MA, 02116, USA.
Panax Clinical Research, Miami Lakes, FL, USA.
Clin Drug Investig. 2017 Nov;37(11):1025-1034. doi: 10.1007/s40261-017-0549-5.
BACKGROUND AND OBJECTIVES: The combination of cromolyn and ibuprofen is being investigated as a treatment for early Alzheimer's disease (AD). This study investigated the pharmacokinetics, safety, and tolerability of cromolyn and ibuprofen co-administration in healthy elderly adult volunteers.
In this open-labeled study, 26 subjects, aged 55-75 years, received co-administration of inhaled cromolyn (single dose 17.1 mg; double dose 34.2 mg total) and oral ibuprofen (single dose 10 mg; double dose 20 mg total). Blood sampling was performed for 6 h after co-administration in all subjects; cerebrospinal fluid (CSF) was collected in three to four subjects per cohort for 4 h following co-administration. Safety parameters, including adverse events (AEs), were monitored throughout the study.
For cromolyn, the mean (±SD) maximum observed concentration (C ) in plasma was 46.69 ± 32.97 and 96.75 ± 46.22 ng/ml after single- and double-dose inhalation, respectively [time to C (t ) ~22 min for each; terminal elimination half-life (t ) ~1.8 h for each]. For ibuprofen, the plasma C was 1090.98 ± 474.64 ng/ml and 2062.96 ± 655.13 ng/ml after single- and double-dose oral administration, respectively (t ~1.6-1.8 h; t ~1.9 h for each). For cromolyn, the CSF C was 0.24 ± 0.08 ng/ml at 3.72 ± 0.70 h after single-dose administration and 0.34 ± 0.17 ng/ml at 3.45 ± 0.95 h after double-dose administration, and for ibuprofen, the CSF C was 3.94 ± 1.29 ng/ml at 2.55 ± 0.96 h after single-dose administration and 8.93 ± 3.29 ng/ml at 3.15 ± 1.05 h after double-dose administration. Three (12%) subjects reported mild or moderate AEs which were unlikely to be related to study drug.
The combination of cromolyn and ibuprofen was safe and well tolerated. The concentrations of cromolyn and ibuprofen observed in the CSF are considered sufficient to titrate the estimated daily amyloid production and the associated inflammatory response in patients with AD.
背景与目的：色甘酸钠和布洛芬联合用药正作为早期阿尔茨海默病（AD）的一种治疗方法进行研究。本研究调查了色甘酸钠和布洛芬在健康老年志愿者中联合用药的药代动力学、安全性和耐受性。
在这项开放标签研究中，26名年龄在55 - 75岁的受试者接受了吸入色甘酸钠（单剂量17.1毫克；总双剂量34.2毫克）和口服布洛芬（单剂量10毫克；总双剂量20毫克）的联合用药。所有受试者在联合用药后6小时进行血样采集；每组三至四名受试者在联合用药后4小时收集脑脊液（CSF）。在整个研究过程中监测包括不良事件（AE）在内的安全参数。
对于色甘酸钠，单次和双次剂量吸入后血浆中观察到的平均（±标准差）最大浓度（Cmax）分别为46.69±32.97和96.75±46.22纳克/毫升[每次达到Cmax的时间（tmax）约为22分钟；每次的终末消除半衰期（t1/2）约为1.8小时]。对于布洛芬，单次和双次剂量口服给药后血浆Cmax分别为1090.98±474.64纳克/毫升和2062.96±655.13纳克/毫升（每次tmax约为1.6 - 1.8小时；每次t1/2约为1.9小时）。对于色甘酸钠，单次给药后3.72±0.70小时脑脊液Cmax为0.24±0.08纳克/毫升，双次给药后3.4
