Delrat P, Paraire M, Jochemsen R
Servier Research and Development Ltd., Windmill road, Fulmer, Slough, SL3 6HH, UK.
Biopharm Drug Dispos. 2002 May;23(4):151-7. doi: 10.1002/bdd.303.
A new modified release (MR) formulation containing 30 mg of gliclazide was developed to obtain a better predictable release of the active principle and to allow once-daily dosing regimen. An absolute bioavailability study was carried out to characterise the performance of the new formulation and the food-effect was also investigated in a separate study. Both studies were single dose, randomised, open label, two way cross over studies with a wash out period between doses. For the bioavailability study, each volunteer received 30 mg of gliclazide given either as a 1 h intravenous infusion or as a 30 mg MR tablet. For the food-effect study, the treatment was given either fasted or 10 min after the start of a standardised Melander breakfast. Blood samples were collected up to 72 h after administrations and plasma samples assayed for gliclazide concentrations using a reverse-phase HPLC method with UV detection. Mean absolute bioavailability of gliclazide was 97% and ranged between 79 and 110% showing complete absorption. A similar moderate to low variability was observed after IV and oral administration showing the MR formulation did not add to the overall variability which is solely due to the disposition parameters, in particular metabolism of gliclazide. No significant difference was observed in t(max), t(1/2z), C(max) and AUC of gliclazide after administration of the 30 mg MR tablet under fasted and fed conditions. In conclusion, after single oral administration of a 30 mg MR tablet, gliclazide was completely absorbed both under fasted and fed conditions. A consistent and optimal release of gliclazide from this formulation leads to a low to moderate overall variability of its pharmacokinetic parameters. Diamicron 30 mg MR can be given without regards to meals i.e. before, during or after breakfast.
开发了一种含有30毫克格列齐特的新型缓释（MR）制剂，以更好地预测活性成分的释放，并实现每日一次的给药方案。进行了一项绝对生物利用度研究，以表征新制剂的性能，并在另一项单独研究中调查了食物效应。两项研究均为单剂量、随机、开放标签、双向交叉研究，剂量之间有洗脱期。在生物利用度研究中，每位志愿者接受30毫克格列齐特，给药方式为1小时静脉输注或30毫克MR片剂。在食物效应研究中，治疗在禁食状态下或在标准化的梅兰德早餐开始10分钟后进行。给药后长达72小时采集血样，并使用带紫外检测的反相高效液相色谱法测定血浆样本中的格列齐特浓度。格列齐特的平均绝对生物利用度为97%，范围在79%至110%之间，表明吸收完全。静脉注射和口服后观察到类似的中低变异性，表明MR制剂并未增加仅由处置参数（特别是格列齐特的代谢）引起的总体变异性。在禁食和进食条件下服用30毫克MR片剂后，格列齐特的t(max)、t(1/2z)、C(max)和AUC未观察到显著差异。总之，单次口服30毫克MR片剂后，格列齐特在禁食和进食条件下均完全吸收。该制剂中格列齐特持续且最佳的释放导致其药代动力学参数的总体变异性低至中度。达美康30毫克MR可以不考虑用餐时间给药，即在早餐前、用餐期间或用餐后给药。
