Departamento Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040 Madrid, Spain.
Eur J Clin Pharmacol. 2012 Jul;68(7):1043-7. doi: 10.1007/s00228-012-1215-8. Epub 2012 Feb 1.
The aim of this study was to compare the systemic exposure of lercanidipine (Zanidip) after oral administration in the fasted state and 15 min before food intake (meals) to investigate if the recommendations in the Summary of Product Characteristics (SPC) with respect to the intake of meals are adequate.
The results of three pilot bioequivalence studies performed to develop a lercanidipine generic product, where Zanidip was administered consistently as reference product in the fasted state or 15 min before a standard breakfast, were compared to estimate the drug–food interaction and the similarity of the methods of administration defined in the SPC.
The ingestion of a standard (non-high-fat, non-high-calorie) meal 15 min after drug intake increased the area under the concentration–time curve (AUC(0-t)) of S-lercanidipine by 1.78-fold [90% confidence interval (CI) 1.48–2.15, P<0.0001] and the maximum concentration (Cmax) of Slercanidipine by 1.82-fold (90% CI 1.46–2.28, P<0.0001). These values are close to the twofold increase that has been described when Zanidip was taken immediately after a carbohydrate-rich meal. Higher levels would be expected with a high-fat, high-calorie meal.
As intake with a carbohydrate-rich meal is not recommended in the SPC of Zanidip because a twofold difference was considered to be clinically relevant, the intake of lercanidipine only 15 min before food intake does not seem to be consistent with this recommendation. The Marketing Authorisation Holder should clarify the dosing instructions in relation to meals and identify a sufficient time-lapse to ensure an exposure similar to that obtained in phase III clinical efficacy studies.
本研究旨在比较口服依泽替米贝（赞安诺）在空腹状态和进食前 15 分钟（餐时）的全身暴露情况，以评估药品说明书中关于进餐的建议是否充分。
我们比较了三项旨在开发依泽替米贝仿制药的生物等效性研究的结果，其中均以赞安诺作为空腹状态下的参比制剂，或在标准早餐前 15 分钟给予，以评估药物-食物相互作用和药品说明书中规定的给药方法的相似性。
进食标准（非高脂肪、高热量）餐 15 分钟后给予药物，可使 S-依泽替米贝的 AUC（0-t）增加 1.78 倍（90%置信区间为 1.48-2.15，P<0.0001），Cmax 增加 1.82 倍（90%置信区间为 1.46-2.28，P<0.0001）。这些值接近赞安诺在进食富含碳水化合物的餐后所描述的两倍增加。如果摄入高脂肪、高热量的食物，预期会有更高的水平。
由于药品说明书中不建议赞安诺与富含碳水化合物的饮食同时服用，因为认为两倍的差异具有临床意义，因此在进食前 15 分钟给予依泽替米贝似乎与这一建议不一致。药品上市许可持有人应澄清与进餐相关的用药说明，并确定足够的时间间隔，以确保与 III 期临床疗效研究中获得的暴露相似。
