Assessment of the pharmacokinetics of co-administered metformin and lobeglitazone, a thiazolidinedione antihyperglycemic agent, in healthy subjects
Assessment of the pharmacokinetics of co-administered metformin and lobeglitazone, a thiazolidinedione antihyperglycemic agent, in healthy subjects
复制标题
DOI：
10.1185/03007995.2012.703131
复制
发表时间：
2012-07-01
影响因子：
2.3
通讯作者：
Yu, Kyung-Sang
中科院分区：
文献类型：
--
作者：
Shin, Donghoon;Kim, Tae-Eun;Yu, Kyung-Sang
目的：洛贝格列酮是一种噻唑烷二酮类抗高血糖药物，可激活过氧化物酶体增殖物激活受体（peroxisome proliferator-activated receptor，PPAR）g，适合单药治疗或与其他抗高血糖药物联合治疗。本研究的主要目的是探讨潜在的药物代谢动力学之间的相互作用洛格列酮和二甲双胍在健康韩国subjects.Methods：一个随机的，开放标签，多剂量，三个治疗，三个阶段，三个序列，交叉研究进行了24名健康韩国男性志愿者。洛格列酮给药后，（0.5 mg/天）和二甲双胍采用液相色谱-串联质谱法（LC-MS）测定药物浓度，临床试验注册号：NCT 01005160。洛格列酮和二甲双胍单独给药的（C-max，（ss）;平均值+/-标准差）分别为29.38 +/- 5.25 ng/mL和1661.84 +/- 471.88 ng/mL;联合给药期间C-max（ss）分别为27.15 +/- 5.75 ng/mL和1779.92 +/- 405.20 ng/mL。洛格列酮和二甲双胍单药给药间隔内的稳态浓度-时间曲线下面积（AUC（tau，SS）;平均值+/-标准差）分别为277.53 +/- 65.25 ng*h/mL和9650.27 +/- 2089.81 ng*h/mL。当洛格列酮和二甲双胍同时给药时，AUC（tau，ss）分别为257.29 +/- 60.61 ng*h/mL和10600.58 +/- 1960.40 ng*h/mL。几何均值比联合用药与洛格列酮单独给药相比，（0.87-0.97; C-max，C-ss）和0.93（0.87-0.99; AUC（tau，ss）），联合用药与二甲双胍单药治疗的相关系数分别为1.09（0.99-1.19; C-max，C-ss）和1.11（1.04-1.19; AUC（tau，ss））。单药治疗和联合治疗耐受性良好，52自我解决，非严重不良事件，报告从17 subjects.Conclusion：洛格列酮没有显着影响二甲双胍的药代动力学，反之亦然，当这两种药物共同管理。洛格列酮可与二甲双胍联合给药，无需调整任一药物的剂量。因此，需要进一步的患者研究来证实这些结果。
Objective:Lobeglitazone as a thiazolidinedione antihyperglycemic agent activates peroxisome proliferator-activated receptor (PPAR) g and may be suitable as monotherapy or in combination with other antihyperglycemic agents. The primary objective of this study was to investigate potential pharmacokinetic interactions between lobeglitazone and metformin in healthy Korean subjects.Methods:A randomized, open-label, multiple-dose, three-treatment, three-period, three-sequence, crossover study was conducted in 24 healthy Korean male volunteers. Serial blood samples were collected after lobeglitazone (0.5 mg/day) and metformin (1000 mg/day) were administered alone or concomitantly for 5 days in each period, and drug concentrations were determined by liquid chromatography-tandem mass spectrometry.Clinical trail registration number:NCT01005160.Results:The steady-state maximum plasma concentrations (C-max, (ss); mean +/- standard deviation) of lobeglitazone and metformin alone were 29.38 +/- 5.25 ng/mL and 1661.84 +/- 471.88 ng/mL, respectively; the C-max, (ss) during co-administration were 27.15 +/- 5.75 ng/mL and 1779.92 +/- 405.20 ng/mL, respectively. The steady-state areas under the concentration-time curves during the dose interval (AUC(tau,SS); mean +/- standard deviation) of sole administration of lobeglitazone and metformin were 277.53 +/- 65.25 ng*h/mL and 9650.27 +/- 2089.81 ng*h/mL, respectively. When lobeglitazone and metformin were administered concomitantly, the AUC(tau, ss) were 257.29 +/- 60.61 ng*h/mL and 10600.58 +/- 1960.40 ng*h/mL, respectively. The geometric mean ratios (90% confidence interval) of co-medication to lobeglitazone alone were 0.92 (0.87-0.97; C-max,C- ss) and 0.93 (0.87-0.99; AUC(tau, ss)), and those for co-medication to metformin monotherapy were 1.09 (0.99-1.19; C-max,C- ss) and 1.11 (1.04-1.19; AUC(tau, ss)). Both monotherapies and combination therapy were well tolerated; 52 self-resolving, non-serious adverse events were reported from 17 subjects.Conclusion:Lobeglitazone did not significantly affect the pharmacokinetics of metformin or vice versa when both drugs were co-administered. Lobeglitazone can be co-administered with metformin without dose adjustment for either agent. Therefore further patient studies are needed to corroborate these results.