Commentary on prevention a possible drug-drug interaction: is concurrent administration of orlistat and pioglitazone increase the risk of durg-induced hepatotoxicity?
Commentary on prevention a possible drug-drug interaction: is concurrent administration of orlistat and pioglitazone increase the risk of durg-induced hepatotoxicity?
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DOI：
10.4103/2008-7802.151825
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发表时间：
2015
影响因子：
2.1
通讯作者：
Moazzam AS
中科院分区：
文献类型：
--
作者：
Emzhik M;Rahimi-Moghaddam P;Ebrahimi SA;Keyhanfar F;Moazzam AS
药物-药物相互作用（ddi）是对公共卫生的新威胁，很难发现。为了预防ddi及其负担，应牢记可能的ddi。我们知道肥胖容易导致胰岛素抵抗和2型糖尿病。因此，联合使用抗肥胖药物和降糖药是很常见的。由于吡格列酮（一种降糖药物）和奥利司他（一种抗肥胖药物）在一些病例中都显示出肝毒性，本研究的目的是评估吡格列酮和奥利司他在人肝细胞系人肝细胞癌（HepG2）细胞中的相互作用，以确定它们对肝毒性的影响。用25 μM吡格列酮（Pio）、20 μM奥利司他（Orl）吡格列酮、奥利司他或两者联合治疗人肝癌细胞。MTT法测定细胞活力。吡格列酮与奥利司他合用导致HepG2细胞活力丧失。单用吡格列酮（25 μM）和奥利他特（20 μM）分别使细胞活力降低约91%和85% (P < 0.05)，两药合用使细胞活力降低约55% （P < 0.001）。发现吡格列酮和奥利司他合用时HepG2细胞活力明显丧失，提示这两种药物不应同时使用，以防止其肝毒性作用，特别是对肝功能障碍患者。
Drug–drug interactions (DDIs) are an emerging threat to public health and are difficult to detect. To prevent DDIs and their burden, the possible DDIs should be kept in mind. We know that the obesity predisposes to the development of insulin resistance and type 2 diabetes. Therefore, combinational uses of antiobesity drugs and glucose-lowering drugs are very common. As the hepatotoxicity of both pioglitazone (an antidiabetic drug) and orlistat (an antiobesity drug) has been shown in some cases, the aim of this study was to evaluate the interaction of pioglitazone and orlistat in human hepatocellular cell line human hepatocellular carcinoma (HepG2) cells to determine their effect on liver toxicity. Human hepatocellular carcinoma cells were treated with 25 μM Pioglitazon (Pio), 20 μM Orlistat (Orl) pioglitazone, orlistat or combination of them. The MTT assay was used to assess cell viability. Pioglitazone and orlistat combination caused a loss of HepG2 cell viability. While pioglitazone (25 μM) and orliatat (20 μM) alone decreased the cell viability around 91% and 85% respectively (notsignificant, P > 0.05), the combination of these two drugs reduced the amount of viable cells to 55% which was significant when compared with each drug alone (P < 0.001). Revealing the significant loss of viability of HepG2 cells in the combination use of pioglitazone and orlistat indicates these two drugs should not be administered at the same time to prevent their hepatotoxic effects especially in patients with liver dysfunction.