0.60 or 1.85 mg Dihydroxybergamottin once weekly

HepG2-GS-3A4 cells, transduced with both hamster glutamine synthetase (GS) gene and human CYP3A4 gene were used for activity evaluation. One-hundred-thousand cells were seeded onto 24-well culture plates and grown to confluence. When cells were nearly confluent, the medium was replaced by 0.3 ml of phosphate-buffered saline (PBS) containing nifedipine (at a concentration of 28.9 mm) as a substrate of CYP3A4 and bergamottin (at a concentration of 0–3.0 mkm) or DHB (at a concentration of 0–5.9 mkm) as an inhibitor of CYP3A4. Samples of 0.1 ml were collected from the solution sequentially at 1 h after incubation at 37°C with 5%CO2. The concentration of oxidised nifedipine in these solutions was measured by high-performance liquid chromatography (HPLC).