title: 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 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.
  
  
  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 (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).
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacology, School of Medicine, Tehran University of Medical Scieneces, Tehran, Iran.
authors: Marjan
authors: M
authors: Emzhik
authors: Department of Pharmacology, School of Medicine, Iran University of Medical Scieneces, Tehran, Iran.
authors: Parvaneh
authors: P
authors: Rahimi-Moghaddam
authors: Department of Pharmacology, School of Medicine, Iran University of Medical Scieneces, Tehran, Iran.
authors: Soltan Ahmad
authors: SA
authors: Ebrahimi
authors: Department of Pharmacology, School of Medicine, Iran University of Medical Scieneces, Tehran, Iran.
authors: Fariborz
authors: F
authors: Keyhanfar
authors: Department of Pharmacology, School of Medicine, Iran University of Medical Scieneces, Tehran, Iran.
authors: Ashraf Sadat
authors: AS
authors: Moazzam
keywords: Drug-drug interaction; human hepatocellular carcinoma cells; liver toxicity; orlistat; pioglitazone