1. The combined effects of the macrolide antibiotics erythromycin, josamycin, clarithromycin and YM17K (3,4'-dideoxy mycaminosyl tylonolide hydrochloride) on in vitro intracellular accumulation of vinblastine or cyclosporine (Cs)A and on the in vivo antitumour activity of vinblastine were investigated using mouse leukaemia P388 cells (P388/S) and anticancer drug-resistant (P388/ADR) cells. These effects were compared with those of a calcium antagonist (verapamil) or immunosuppressants (FK506 and CsA). 2. All tested macrolide antibiotics increased the accumulation of both vinblastine and CsA in P388/ADR cells in a dose-dependent manner, but their potency was lower than that of verapamil, CsA or FK506. 3. When vinblastine (200 microg/kg) was administered intraperitoneally with each of the macrolide antibiotics (10 or 100 mg/kg) or with verapamil (25 mg/kg) once a day for 10 days in P388/ADR-bearing mice, combined effects of vinblastine with the macrolide antibiotics (erythromycin, clarithromycin and YM17K) or verapamil were observed. 4. The present study suggests that macrolide antibiotics may overcome anticancer drug resistance by inhibiting the binding of vinblastine or CsA to P-glycoprotein in P388/ADR cells. 5. We believe that these results are encouraging for combination chemotherapy to overcome P-glycoprotein-dependent anticancer drug-resistant tumours in clinical practice.
1992-08-01·Antimicrobial Agents and Chemotherapy2区 · 医学
In vitro activity of MC-352, a new 16-membered macrolide
2区 · 医学
作者: Chin, Nai Xun ; Neu, Harold C.
The in vitro activity of MC-352, 3,4'-dideoxy-5-O-mycaminosyltylonolide, was compared with those of erythromycin, clarithromycin, and rokitamycin. The MC-352 MIC90 (MIC for 90% of isolates) for erythromycin-susceptible Staphylococcus aureus and Staphylococcus epidermidis was less than or equal to 1 microgram/ml, similar to those of the other agents. The MC-352 MIC50 for erythromycin-resistant S. aureus was 2 micrograms/ml, similar to that of rokitamycin. The MC-352 MIC90 (0.12 micrograms/ml) for Streptococcus pyogenes was similar to those of erythromycin and clarithromycin and superior to that of rokitamycin, and the MC-352 MIC90 for group B, C, and G streptococci was 0.25 microgram/ml. MC-352 and clarithromycin had an MIC90 of 0.12 microgram/ml for Streptococcus pneumoniae. Erythromycin-susceptible Enterococcus faecalis was inhibited by MC-352 at 1 microgram/ml, but the MIC for constitutively erythromycin-resistant isolates was greater than 16 micrograms/ml. Legionella pneumophila was inhibited by less than or equal to 0.25 microgram/ml. MC-352 was the most active agent against Bacteroides fragilis, with an MIC90 of 8 micrograms/ml, and was more active than the other agents against Haemophilus influenzae, with an MIC90 of 4 micrograms/ml. Moraxella spp. were inhibited by MC-352 at less than or equal to 0.25 microgram/ml. The MIC90 for Escherichia coli, Klebsiella pneumoniae, and Salmonella, Shigella, Yersinia, Enterobacter, Citrobacter, and Serratia spp. was greater than or equal to 32 micrograms/ml. MC-352 was bactericidal for S. pyogenes and S. pneumoniae, and its activity was not altered by human serum.