Commentary on Prevention a Possible Drug–Drug Interaction: Is Concurrent Administration of Orlistat and Pioglitazone Increase the Risk of Durg‑Induced Hepatotoxicity?

Abstract

Background: Drug–drug interactions  (DDIs) are an emerging threat to public health and are diffcult 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.
Methods: 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.
Results: 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 (notsignifcant, P > 0.05), the combination of these two drugs reduced the amount of viable cells to 55% which was signifcant when compared with each drug alone (P < 0.001).
Conclusions: Revealing the signifcant 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.
Keywords: Drug‑drug interaction, human hepatocellular carcinoma cells, liver toxicity, orlistat, pioglitazone