Syed Shariq A, Kamimori Gary H, Kelly William, Eddington Natalie D
Pharmacokinetics-Biopharmaceutics Laboratory, Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, AHB 540A, 100 Penn Street, 21201, USA.
Biopharm Drug Dispos. 2005 Dec;26(9):403-9. doi: 10.1002/bdd.469.
The purpose of this study was to examine the pharmacokinetics of three doses of caffeine administered as Stay Alert chewing gum in a multiple dose regimen.
A double-blind, parallel randomized, four-treatment study design was employed. The treatment groups were: 50, 100 and 200 mg caffeine and placebo. Subjects were 48 (n = 12 per group), healthy, non-smoking, males and females who had abstained from caffeine ingestion for at least 20 h prior to dosing, who were randomly assigned to the treatment groups. Caffeine was administered at 2,400, 0200 and 0400 h depending on the treatment group. Blood samples were collected pre-dose and at 5, 15, 30, 45, 60, 75, 90 and 105 min after each caffeine dose. Samples were also collected at 7.5, 8.5 and 18 h after the last dose of caffeine. Plasma caffeine levels were analysed by a validated UV-HPLC method.
The mean T(max) after the third dosing ranged from 0.37 to 1.12 h. C(max) for 50, 100 and 200 mg was 2.69, 3.45 and 6.33 mg/l, respectively. AUC(inf) for 50, 100 and 200 mg group was 33.2, 46.94 and 86.94 mg/l * h, respectively. AUC(inf) values suggested a dose proportionate increase. Dose normalized C(max) and AUC(0-tau) values across doses were not significantly different, suggesting linearity was maintained after multiple doses of the Stay Alert chewing gum. There were no group related differences in elimination.
The results suggest that caffeine administered in the gum formulation (Stay Alert chewing gum) via a multiple dosing regimen provides an effective and convenient means of maintaining effective concentrations of caffeine that would in some operational scenarios be desirable for maintaining alertness and performance in sleep deprived individuals.
本研究的目的是考察在多剂量给药方案中，作为“保持警觉”口香糖服用的三种剂量咖啡因的药代动力学。
采用双盲、平行随机、四治疗组研究设计。治疗组分别为：50毫克、100毫克和200毫克咖啡因以及安慰剂组。受试者共48名（每组12名），为健康、不吸烟的男性和女性，给药前至少20小时未摄入咖啡因，随机分配至各治疗组。根据治疗组不同，咖啡因分别在02:00、04:00和06:00给药。在每次咖啡因给药前及给药后5、15、30、45、60、75、90和105分钟采集血样。在最后一剂咖啡因给药后7.5、8.5和18小时也采集血样。采用经过验证的紫外-高效液相色谱法分析血浆咖啡因水平。
第三次给药后的平均达峰时间（T(max)）为0.37至1.12小时。50毫克、100毫克和200毫克剂量的峰浓度（C(max)）分别为2.69、3.45和6.33毫克/升。50毫克、100毫克和200毫克组的药时曲线下面积（AUC(inf)）分别为33.2、46.94和86.94毫克/升·小时。AUC(inf)值显示呈剂量比例增加。各剂量下剂量标准化的C(max)和AUC(0-tau)值无显著差异，表明多次服用“保持警觉”口香糖后维持了线性关系。各治疗组在消除方面无相关差异。
结果表明，通过多剂量给药方案以口香糖剂型（“保持警觉 ”口香糖）服用咖啡因，可提供一种有效且便捷的方式来维持咖啡因的有效浓度，在某些操作场景中，这对于保持睡眠不足个体的警觉性和工作表现是可取的。
