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Antimicrobial Agents and Chemotherapy, June 2000, p. 1697-1700, Vol. 44, No. 6
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Interactions of Ofloxacin and Erythromycin with the Multidrug Resistance Protein (MRP) in MRP-Overexpressing Human Leukemia Cells

Kenji Terashi,1,2,dagger Mikio Oka,1,* Hiroshi Soda,1 Minoru Fukuda,1 Shigeru Kawabata,1 Katsumi Nakatomi,1 Ken Shiozawa,1 Takashi Nakamura,1 Kazuhiro Tsukamoto,1 Yuji Noguchi,1 Mitsuhiro Suenaga,1 Chuwa Tei,2 and Shigeru Kohno1

Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501,1 and First Department of Internal Medicine, Kagoshima University Faculty of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520,2 Japan

Received 11 August 1999/Returned for modification 23 December 1999/Accepted 3 March 2000

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.

* Corresponding author. Mailing address: Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan. Phone: 81-(95)-849-7274. Fax: 81-(95)-849-7285. E-mail: okamikio{at}net.nagasaki-u.ac.jp.

dagger Present address: First Department of Internal Medicine, Kagoshima University Faculty of Medicine, Kagoshima, Japan.

Antimicrobial Agents and Chemotherapy, June 2000, p. 1697-1700, Vol. 44, No. 6
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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