Tolerability and pharmacokinetics of inhaled bimosiamose disodium in healthy males.
Tolerability and pharmacokinetics of inhaled bimosiamose disodium in healthy males.
复制标题
健康男性吸入二摩糖二钠的耐受性和药代动力学。
DOI：
--
复制
发表时间：
2007
影响因子：
3.4
通讯作者：
G. Wolff
中科院分区：
文献类型：
--
作者：
M. Meyer;K. Beeh;J. Beier;D. Beyer;E. Aydt;R. Zahlten;B. Jilma;G. Wolff
旨在
这些首次人体研究的目的是研究通过吸入给药的双唾液酸葡萄糖二钠（TBC 1269 Z）的耐受性和药代动力学。
方法
在健康男性中进行了两项随机、双盲、安慰剂对照I期试验。在一项单次给药递增研究中，48例受试者接受2-140 mg双莫阿糖二钠吸入给药，在一项多次给药研究中，32例受试者接受8-70 mg双莫阿糖二钠每日两次给药。在两项研究中，通过雾化器在15分钟内给药4 ml药物溶液。记录不良事件、生命体征、ECG、临床实验室参数和1秒用力呼气容积（FEV（1））数据，并进行鼻咽检查以确定安全性和耐受性。采集血液用于测定双莫司阿莫糖的血浆浓度。
结果
所有受试者均完成研究。未发生死亡或严重不良事件。在吸入双莫沙糖二钠后，剂量递增研究中发生了11例轻度不良事件，多次给药研究中发生了34例。在剂量递增研究的最高剂量（140 mg）下，不良事件更频繁。对于安慰剂治疗，在安慰剂治疗后的剂量递增研究中观察到1起中度不良事件，在多次给药研究中发生8起轻度和3起中度不良事件。在血浆中检测到双莫司（最大浓度64 ng ml（-1））仅在剂量>或=50 mg每日两次和105 mg每日一次给药时。对于最高剂量，在多次给药研究的整个治疗期间，确定AUC的中位值为5746 h ng ml（-1）。
结论
结果表明，健康男性单次和多次吸入高达70 mg的双莫阿糖二钠耐受性良好。吸入后的全身生物利用度较低。
AIMS
The aim of these first-in-human studies was to investigate the tolerability and the pharmacokinetics of bimosiamose disodium (TBC1269Z) administered by inhalation.
METHODS
Two randomized, double-blind, placebo-controlled Phase I trials were performed in healthy males. In a single-dose escalating study 48 subjects received doses of 2-140 mg bimosiamose disodium by inhalation and in a multiple-dose study 32 subjects received 8-70 mg bimosiamose disodium twice daily. In both studies 4 ml of the drug solution was administered via nebulizer over 15 min. Adverse events, vital signs, ECG, clinical laboratory parameters and forced expiratory volume in 1 s (FEV(1)) data were recorded and nasopharyngeal examinations were performed to address the safety and tolerability. Blood was collected for the determination of plasma concentrations of bimosiamose.
RESULTS
All subjects completed the study. No deaths or severe adverse events occurred. Eleven mild adverse events occurred in the dose-escalation study and 34 in the multiple-dose study after inhalation of bimosiamose disodium. Adverse events were more frequent at the highest dose (140 mg) of the dose-escalation study. For placebo treatment one moderate adverse event was observed in the dose-escalation study after placebo treatment, eight mild and three moderate adverse events occurred in the multiple-dose study. Bimosiamose was detected in plasma (maximum concentration 64 ng ml(-1)) only at doses > or =50 mg given twice daily and 105 mg once daily. For the highest dose a median value of 5746 h ng ml(-1) was determined for the AUC over the entire period of treatment of the multiple-dose study.
CONCLUSION
The results suggest that single and multiple inhalation of bimosiamose disodium up to 70 mg is well tolerated in healthy males. Systemic bioavailability after inhalation is low.
小分子多重选择素抑制剂可逆转与出血相关的肺趋化因子的上调。
影响因子：
5.2
作者：
Ramos-Kelly,JR;Toledo-Pereyra,LH;Jordan,JA;Rivera-Chavez,FA;Dixon,RA;Ward,PA
通讯作者：
Ward,PA