Borleffs J C, Bosschaert M, Vrehen H M, Schneider M M, van Strijp J, Small M K, Borkett K M
Department of Internal Medicine, University Hospital, Utrecht, The Netherlands.
Clin Ther. 1998 Jul-Aug;20(4):722-36. doi: 10.1016/s0149-2918(98)80135-5.
The safety profile, tolerability, pharmacodynamics, and pharmacokinetics of four doses of recombinant human granulocyte colony-stimulating factor (filgrastim) were assessed in healthy volunteers in a double-masked, placebo-controlled, parallel-group trial. Healthy subjects received subcutaneous injections of filgrastim 75 microg (n = 8), 150 microg (n = 4), 300 microg (n = 4), 600 microg (n = 8), or placebo (n = 6) daily for 10 consecutive days. Blood samples were drawn daily immediately before the injection and on days 1 and 10 serially throughout the day. Increased absolute neutrophil counts (ANCs) were seen within 90 minutes of drug administration in subjects in all dose groups, peaking approximately 12 hours after administration. This increase was dose related in subjects in the three lower dose groups. The time to peak ANC on day 10 was approximately 9 hours, with a daily ANC profile in all four dose groups that was similar to the profile on day 1. In all dose groups, ANCs were near baseline within 48 hours of discontinuation of filgrastim. Mild, reversible thrombocytopenia was reported in 4 of 10 subjects in the highest dose group. Two subjects in the filgrastim 600-microg group were withdrawn for adverse events. Filgrastim had a good safety profile and caused dose-related increases in ANC when administered to healthy volunteers for up to 10 days.
在一项双盲、安慰剂对照、平行组试验中，对健康志愿者评估了四剂重组人粒细胞集落刺激因子（非格司亭）的安全性、耐受性、药效学和药代动力学。健康受试者连续10天每天皮下注射75微克非格司亭（n = 8）、150微克（n = 4）、300微克（n = 4）、600微克（n = 8）或安慰剂（n = 6）。每天在注射前即刻采集血样，并在第1天和第10天全天连续采集。所有剂量组的受试者在给药后90分钟内可见绝对中性粒细胞计数（ANC）增加，给药后约12小时达到峰值。在三个较低剂量组的受试者中，这种增加与剂量相关。第10天ANC达到峰值的时间约为9小时，所有四个剂量组的每日ANC曲线与第1天的曲线相似。在所有剂量组中，停用非格司亭后48小时内ANC接近基线水平。最高剂量组的10名受试者中有4名报告有轻度、可逆性血小板减少。非格司亭600微克组有两名受试者因不良事件退出试验。非格司亭具有良好的安全性，在健康志愿者中给药长达10天时可引起与剂量相关的ANC增加。
