Bioavailability of repaglinide, a novel antidiabetic agent, administered orally in tablet or solution form or intravenously in healthy male volunteers.
Bioavailability of repaglinide, a novel antidiabetic agent, administered orally in tablet or solution form or intravenously in healthy male volunteers.
复制标题
瑞格列奈（一种新型抗糖尿病药）的生物利用度，以片剂或溶液形式口服或静脉注射给健康男性志愿者。
DOI：
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复制
发表时间：
1998
影响因子：
0.8
通讯作者：
Su Ca
中科院分区：
文献类型：
--
作者：
Hatorp;S. Oliver;Su Ca
目标
瑞格列奈是一种新型餐时血糖调节剂（PGR），用于治疗 2 型糖尿病。为了研究口服瑞格列奈后的受试者变异性，并确定口服或静脉给药后瑞格列奈的相对和绝对生物利用度，进行了两项单中心、开放标签、随机、交叉临床研究。
主题和方法
研究 1 在 24 名健康男性受试者（年龄 18 至 49 岁）中进行，他们接受瑞格列奈 2 mg（片剂或口服溶液），每次 4 次，每次两次，间隔至少 7 天。研究2是在12名健康男性受试者（年龄18至45岁）中进行的，他们接受瑞格列奈2 mg，作为片剂或在15分钟内静脉输注，每次2次，洗脱期为7-10天。
结果
在研究 1 中，瑞格列奈 2 mg（片剂或口服溶液形式）的受试者体内 AUC 和 Cmax 变化没有显着差异。然而，片剂的 t(max) 和平均停留时间 (MRT) 的受试者体内差异显着 (p = 0.001) 大于口服溶液。口服给药后，AUC 的受试者间变异 (CV) 范围为 44.7% 至 62.1%。瑞格列奈的相对生物利用度（AUC（片剂）/AUC（口服溶液））为110%（95% CI，103%-117%）。在研究 2 中，相对于静脉输注相同剂量的瑞格列奈片剂的绝对生物利用度为 62.5%（95% CI，49.2%-79.5%）。
结论
两项研究都没有证据表明片剂配方会导致瑞格列奈血清谱发生更大的变化。结论是，在禁食条件下口服或静脉注射时，瑞格列奈在健康受试者中被迅速吸收和消除，并且瑞格列奈在片剂和口服溶液制剂中的总利用度相似，尽管片剂制剂的吸收速率较慢。
OBJECTIVE
Repaglinide is a novel prandial glucose regulator (PGR) for the treatment of type 2 diabetes. In order to investigate subject variability following oral administration of repaglinide, and to determine the relative and absolute bioavailabilities of repaglinide following oral or intravenous administration, two single-centre, open-label, randomized, crossover clinical studies were conducted.
SUBJECTS AND METHODS
Study 1 was conducted in 24 healthy male subjects (aged 18 to 49 years), who received repaglinide 2 mg, as either tablet or oral solution, twice each on 4 separate occasions at least 7 days apart. Study 2 was conducted in 12 healthy male subjects (aged 18 to 45 years), who received repaglinide 2 mg, either as a tablet or as an intravenous infusion over 15 minutes, once each on 2 separate occasions, with a washout period of 7-10 days.
RESULTS
In study 1 there was no significant difference between administration of repaglinide 2 mg, in either tablet or oral solution form with regard to intrasubject variation in AUC and Cmax. However, the intrasubject variation in t(max) and mean residence time (MRT) was significantly (p = 0.001) larger for the tablets than for the oral solution. Intersubject variation (CV) in AUC ranged from 44.7% to 62.1% after oral administration. The relative bioavailability of repaglinide (AUC(tablet)/AUC(oral solution)) was 110% (95% CI, 103%-117%). In study 2 the absolute bioavailability of repaglinide administered as a tablet was 62.5% (95% CI, 49.2%-79.5%) relative to an intravenous infusion of the same dose.
CONCLUSION
There was no evidence from either study that the tablet formulation led to greater variation in serum profiles of repaglinide. It was concluded that repaglinide is rapidly absorbed and eliminated in healthy subjects when administered orally or intravenously under fasting conditions, and that the total availability of repaglinide is similar in the tablet and oral solution formulations, though that the rate of absorption is slower for the tablet formulation.