Effects of genetic polymorphisms on the OCT1 and OCT2-mediated uptake of ranitidine
Fig 3
Genotype-dependence of the ranitidine inhibitory potency.
We compared the potency of ranitidine to inhibit the uptake of metformin (A), morphine (B), ASP+ (C), and MPP+ (D) by the reference and OCT1*2 alleles. HEK293 T-REx™ cells overexpressing the reference or OCT1*2 allele were incubated for 2 min with 0.1 μM morphine (A), 100 μM metformin (B), 1 μM ASP+ (C), or 0.1 μM MPP+ (D) in the presence of increasing concentrations of ranitidine. The uptake is represented as percentage of OCT1-mediated ranitidine uptake without inhibition. Shown are means and standard error of the means of at least three independent experiments and the half maximal inhibitory concentrations (IC50) were calculated. The clinically relevant concentrations of ranitidine in plasma, portal vein, and gastrointestinal (GI) tract are highlighted in grey. The plasma concentrations were estimated based on the Cmax of ranitidine after an oral administration of a single dose of 150 to 300 mg ranitidine [5, 8]. The concentrations in the portal vein were estimated as described elsewhere [51, 52]. The concentrations in the GI tract were estimated supposing that 150 to 300 mg ranitidine are solved in 686 ml GI fluid volume [54].