Effect of the PPARα-activator gemfibrozil on whole blood drug transporter gene expression in humans

Gemfibrozil is a fibric acid derivative used in the treatment of dyslipidemia. It activates peroxisome proliferator activated receptor α (PPARα) and alters lipoprotein metabolism gene expression. PPARα may also regulate the expression of drug disposition genes (e.g., CYP3A4). The aim of this study was to investigate possible effects of gemfibrozil on drug transporter gene expression in human whole blood. In a randomized crossover study, 10 healthy volunteers took 600 mg gemfibrozil or placebo twice daily for 6 days (Filppula et al. 2013). On the morning of day 3, a venous blood RNA sample was collected from each participant into a PaxGene® tube. The expression of 18 ABC, 24 SLC and 10 SLCO transporters was investigated using reverse transcription quantitative real-time PCR (RT-qPCR) with OpenArray® technology on a QuantStudio™ 12 K Flex Real-Time PCR system (Life Technologies, Paisley, UK). FPGS, TRAP1, DECR1 and PPIB served as reference genes. A total of 31 transporters, including 15 ABC transporters, 13 SLC transporters and 3 SLCO transporters were significantly expressed in whole blood during the placebo phase. Gemfibrozil appeared to alter the expression of three transporters. The expression of SLCO3A1 was increased by 34% by gemfibrozil (P=0.004), but gemfibrozil reduced the expression of ABCG2 and ABCC3 by 31% (P=0.018) and 50% (P=0.045), respectively. However, none of the differences remained statistically significant after correction for multiple testing. In conclusion, these data suggest that gemfibrozil might alter the gene expression of certain drug transporters in human blood