The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers
The rate of absorption and relative bioavailability of caffeine administered in chewing gum versus capsules to normal healthy volunteers
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DOI：
10.1016/s0378-5173(01)00958-9
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发表时间：
2002-03-02
影响因子：
5.8
通讯作者：
Eddington, ND
中科院分区：
文献类型：
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作者：
Kamimori, GH;Karyekar, CS;Eddington, ND
目的：本研究的目的是评价Stay Alert（R）口香糖和胶囊制剂中咖啡因的吸收率和相对生物利用度。方法：这是一项双盲、平行、随机、7种治疗方法的研究。治疗组为：50、100和200 mg口香糖，50、100和200 mg胶囊和安慰剂。受试者包括84名（每组n = 12名）;健康、不吸烟、在给药前至少20小时内戒断咖啡因摄入的男性，并被随机分配至治疗组。在给药前和给药后5、15、25、35、45、55、65、90 min和2、3、4、6、8、12、16和29 h采集血样。通过经验证的UV-HPLC方法分析血浆咖啡因水平。结果：咀嚼胶组的平均Tmax范围为44.2 - 80.4 min，胶囊组为84.0-120.0 min。与胶囊组相比，口香糖组的汇总数据的Tmax显著较低（P < 0.05）。200 mg胶囊与200 mg口香糖的Tmax差异显著（P < 0.05）。咀嚼胶组的平均k（a）值范围为3.21 - 3.96 h（-1），胶囊组的平均k（a）值范围为1.29 - 2.36 h（-1）。在50、100和200 mg剂量后，咀嚼胶制剂的相对生物利用度分别为64、74和77%。当标准化为从口香糖释放的总药物（85%）时，50、100和200 mg剂量的相对生物利用度分别为75、87和90%。在各剂量下，咀嚼胶和胶囊制剂的C-max和AUC（inf）比较无统计学差异。在各剂量水平内，C-max无显著制剂相关差异。口香糖或胶囊后，咖啡因的消除没有显着差异。结论：结果表明，药物从口香糖制剂中吸收的速率明显更快，可能表明通过颊粘膜吸收。此外，对于100和200 mg组，口香糖和胶囊制剂向体循环提供的咖啡因量几乎相当。这些发现表明，作为口香糖制剂递送的咖啡因的药理学作用可能更早开始，这在期望快速逆转由睡眠丧失引起的警觉性和表现缺陷的情况下是有利的。(C)2002 Elsevier Science B. V.保留所有权利。
Objective:The purpose of this study was to evaluate the rate of absorption and relative bioavailability of caffeine from a Stay Alert(R) chewing gum and capsule formulation. Methods: This was a double blind, parallel, randomized, seven treatment study. The treatment groups were: 50, 100, and 200 mg gum, 50, 100, and 200 mg capsule, and a placebo. Subjects consisted of 84 (n = 12 per group); healthy, non-smoking, males who had abstained from caffeine ingestion for at least 20 h prior to dosing and were randomly assigned to the treatment groups. Blood samples were collected pre-dose and at 5, 15, 25, 35, 45, 55, 65, 90 min and 2, 3, 4, 6, 8, 12, 16 and 29 h post administration. Plasma caffeine levels were analyzed by a validated UV-HPLC method. Results: Mean T-max for the gum groups ranged from 44.2 to 80.4 min as compared with 84.0-120.0 min for the capsule groups. The T-max for the pooled data was significantly lower (P < 0.05) for the gum groups as compared with the capsule groups. Differences in T-max were significant for the 200 mg capsule versus 200 mg gum (P < 0.05). The mean k(a) values for the gum group ranged from 3.21 to 3.96 h(-1) and for the capsule groups ranged from 1.29 to 2.36 h(-1). Relative bioavailability of the gum formulation after the 50, 100 and 200 mg dose was 64, 74 and 77%, respectively. When normalized to the total drug released from the gum (85%), the relative bioavailability of the 50, 100 and 200 mg dose were 75, 87, and 90%, respectively. No statistical differences were found for C-max and AUC(inf) for comparisons of the gum and capsule formulations at each dose. Within each dose level, there were no significant formulation related differences in C-max. No significant differences were observed in the elimination of caffeine after the gum or capsule. Conclusions: The results suggest that the rate of drug absorption from the gum formulation was significantly faster and may indicate absorption via the buccal mucosa. In addition, for the 100 and 200 mg groups, the gum and capsule formulations provide near comparable amounts of caffeine to the systemic circulation. These findings suggest that there may be an earlier onset of pharmacological effects of caffeine delivered as the gum formulation, which is advantageous in situations where the rapid reversal of alertness and performance deficits resulting from sleep loss is desirable. (C) 2002 Elsevier Science B.V. All rights reserved.