Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla, Thailand.
Clin Drug Investig. 2003;23(4):273-80. doi: 10.2165/00044011-200323040-00007.
To compare the bioavailability of two 15mg ambroxol lozenges with a commercial 30mg ambroxol tablet.
Open-label, two-way crossover study.
Each formulation was randomly administered to 20 healthy Thai volunteers (ten male and ten female) with a 1-week washout period between formulations. After administration, serial blood samples were collected over a 24-hour period and the plasma concentration of ambroxol was subsequently measured using high performance liquid chromatography with ultraviolet detection after liquid-liquid extraction. Pharmacokinetic parameters were analysed by a noncompartmental pharmacokinetic model and compared between formulations using analysis of variance with a significance level of 0.05.
The point estimates (90% CI) of the area under the plasma concentration-time curve (AUC) and peak plasma concentration (C(max)) ratios between lozenge and commercial tablet were 1.07 (0.89 to 1.28) and 1.20 (1.04 to 1.40), respectively. The point estimate (90% CI) of the difference between formulations for time to C(max) was 0.40 (-0.20 to 1.00).
The two formulations under test were not bioequivalent based on the stipulated bioequivalence criteria. The bioavailability from the ambroxol lozenge might be better, since the 90% CI of the AUC(0-infinity) fell outside the bioequivalence range, and its range was narrower. The difference in rate of absorption was not conclusive because ambroxol was delivered from the lozenge by two parallel processes, namely absorption via oral and gastrointestinal mucosa. The additional oral mucosal absorption might not only contribute more absorption but also introduce variability compared with that of tablet administration. The relative importance of oral versus gastrointestinal mucosal absorption of ambroxol from the lozenge formulation, and the clinical significance of this, requires further study.
比较两种 15mg 氨溴索口含片与一种市售 30mg 氨溴索片的生物利用度。
开放标签、两交叉研究。
每种制剂均随机分配给 20 名健康的泰国志愿者（男女各 10 名），每种制剂之间有 1 周洗脱期。给药后，在 24 小时内采集系列血样，并用高效液相色谱法结合紫外检测法经液-液萃取后测定氨溴索的血浆浓度。采用非房室药代动力学模型分析药代动力学参数，并采用方差分析比较两种制剂，以 0.05 为显著性水平。
口含片与市售片剂的血浆浓度-时间曲线下面积（AUC）和峰血浆浓度（C(max))比值的点估计值（90%CI）分别为 1.07（0.89 至 1.28）和 1.20（1.04 至 1.40）。两种制剂间 C(max)达峰时间的点估计值（90%CI）差值为 0.40（-0.20 至 1.00）。
根据规定的生物等效性标准，两种受试制剂不等效。氨溴索口含片的生物利用度可能更好，因为 AUC(0-无穷）的 90%CI 落在生物等效性范围之外，且其范围更窄。吸收速率的差异没有定论，因为氨溴索通过两种平行过程从口含片释放，即通过口腔和胃肠道黏膜吸收。与片剂给药相比，口腔黏膜吸收可能不仅贡献更多的吸收，而且还会引入变异性。氨溴索从口含片制剂中的口腔与胃肠道黏膜吸收的相对重要性及其临床意义需要进一步研究。
