Interactions of ofloxacin and erythromycin with the multidrug resistance protein (MRP) in MRP-overexpressing human leukemia cells

Antimicrob Agents Chemother. 2000 Jun;44(6):1697-700. doi: 10.1128/AAC.44.6.1697-1700.2000.

Abstract

To investigate interactions between the multidrug resistance protein (MRP) and antimicrobial agents, we examined the effects of 12 agents on vincristine sensitivity and efflux of the calcein acetoxy-methyl ester (calcein-AM) of a MRP substrate in MRP-overexpressing cells. Only ofloxacin and erythromycin enhanced sensitivity with increased intracellular vincristine accumulation and inhibited the calcein-AM efflux. Our findings suggest that the two agents are possible MRP substrates and may competitively inhibit MRP function as a drug efflux pump.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Drug Interactions*
  • Erythromycin / pharmacology*
  • Erythromycin / therapeutic use
  • Fluoresceins / metabolism
  • Genes, MDR*
  • Humans
  • Leukemia / drug therapy*
  • Leukemia / genetics
  • Leukemia / metabolism
  • Ofloxacin / pharmacology*
  • Ofloxacin / therapeutic use
  • Tumor Cells, Cultured
  • Vincristine / pharmacology*
  • Vincristine / therapeutic use

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Antineoplastic Agents, Phytogenic
  • Fluoresceins
  • Vincristine
  • Erythromycin
  • Ofloxacin
  • fluorexon