In vitro interaction of mezlocillin with fluorouracil and mitomycin

The interaction of mezlocillin (Baypen) with either fluorouracil (5-fluorouracil, 5-FU) or mitomycin was tested in vitro by incubating colorectal carcinoma cell line HT 29 with varying concentrations of mezlocillin, 5-FU, mitomycin and the combinations of mezlocillin + 5-FU and mezlocillin + mitomycin. Inhibition of colony growth in soft agar of treated compared with untreated cells was used as an in vitro response parameter. Concentration ranges were representative for regional chemotherapy with mitomycin or 5-FU and perioperative antibiotic therapy with mezlocillin. Mezlocillin, 5-FU and mitomycin showed dose-dependent inhibition of colony growth. Mezlocillin produced a maximal toxicity of 16% at 1000 micrograms/ml. Toxicity of 5-FU was reduced by addition of mezlocillin. The increase of colony growth after coincubation of mezlocillin with 5-FU (compared to cells treated with 5-FU alone) at a mezlocillin concentration of 10 micrograms/ml was 47% to 116%, at 100 micrograms/ml 44% to 132%, depending on the 5-FU test concentrations. The 5-FU toxicity in some instances was nearly abolished. There was no interaction between mezlocillin and mitomycin. The interference of mezlocillin with 5-FU-toxicity should be respected in case of combined perioperative antitumor and antibiotic therapy with 5-FU mezlocillin. Similar interactions with related antibiotics cannot be excluded.