Zuin M, Podda M, Selmi C, Giorgini A, Zermiani P, Mandelli G, Sacchetta A C, Candiani C
Ospedale S. Paolo, Chair of Internal Medicine, Università degli Studi di Milano, Italy.
Arzneimittelforschung. 2000 Sep;50(9):837-42. doi: 10.1055/s-0031-1300298.
Ibuprofen (CAS 15687-27-1) is a nonsteroidal antiinflammatory drug endowed with analgesic, antiinflammatory and antipyretic activity. The main side effect of ibuprofen and nonsteroidal antiinflammatory agents is addressed to disturbances of the gastrointestinal tract, like gastric pyrosis, gastric and intestinal damage. A pharmaceutical formulation of ibuprofen in fast melting tablets consisting in gastroprotected microgranules to be ingested without concomitant water intake (Cibalginadue Fast, hereinafter referred to as test) was compared in this trial with a formulation of ibuprofen in tablets (reference) on 18 healthy volunteers in terms of gastrointestinal and general tolerability. Both the formulations are present on the market. The two formulations were administered according to a two-period, two-formulation, two-sequence, cross-over design in repeated dose regimen to steady state with wash-out. The dose was 400 mg (2 strengths) b.i.d. over 7 days. Before, during and after each study period general tolerability was carefully checked from blood/urine biochemical parameters, adverse events experienced and vital signs. The target parameters were the gastric permeability to sucrose and the intestinal permeability to lactulose and mannitol, which were administered orally and assayed in the urine excreted during a 6-h period. Urinary excretion > 0.15% of sucrose and > 0.04 of the lactulose to mannitol ratio are considered expression of increased gastric and intestinal permeability, respectively. Three volunteers treated with the reference showed an increased gastric permeability > 0.15%. Neither other gastric nor intestinal increased permeability was detected. Occult blood in faeces was negative in all the cases. The incidence of adverse effects experienced was higher with the reference (9 volunteers) than with the test (5 volunteers). In details gastric pyrosis was experienced by six volunteers treated with the reference and only by two volunteers treated with the test. The whole tolerability was better with the test formulation than with the reference, even if these differences did not reach any statistically significant degree. The better tolerability of the test was attributed to its gastroprotection.
布洛芬（CAS 15687-27-1）是一种具有镇痛、抗炎和解热活性的非甾体抗炎药。布洛芬和非甾体抗炎药的主要副作用是针对胃肠道紊乱，如胃灼热、胃和肠道损伤。在本试验中，将一种布洛芬速溶片的药物制剂（Cibalginadue Fast，以下简称试验制剂）与一种布洛芬片剂制剂（参比制剂）在18名健康志愿者身上就胃肠道耐受性和总体耐受性进行了比较。两种制剂均已上市。两种制剂按照两周期、两制剂、两序列、交叉设计的重复给药方案给药至稳态并进行洗脱期。剂量为400mg（两种规格），每日两次，共7天。在每个研究期之前、期间和之后，通过血液/尿液生化参数、经历的不良事件和生命体征仔细检查总体耐受性。目标参数是蔗糖的胃通透性以及乳果糖和甘露醇的肠道通透性，它们通过口服给药，并在6小时内排出的尿液中进行测定。蔗糖尿排泄率>0.15%以及乳果糖与甘露醇的比值>0.04分别被认为是胃和肠道通透性增加的表现。三名接受参比制剂治疗的志愿者出现了胃通透性增加>0.15%。未检测到其他胃或肠道通透性增加的情况。所有病例粪便潜血均为阴性。接受参比制剂治疗的志愿者（9名）出现不良反应的发生率高于接受试验制剂治疗的志愿者（5名）。具体而言，六名接受参比制剂治疗的志愿者出现了胃灼热，而接受试验制剂治疗的志愿者中只有两名出现胃灼热。试验制剂的总体耐受性优于参比制剂，即使这些差异未达到任何统计学显著程度。试验制剂更好的耐受性归因于其胃保护作用。
