CHANTEUX H, MICHOT J, SERAL C, VAN BAMBEKE F, MINGEOT-LECLERCQ M, TULKENS PM; Interscience Conference on Antimicrobial Agents and Chemotherapy (42nd : 2002 : San Diego, Calif.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2002 Sep 27-30; 42: abstract no. A-488.

Univ. catholique de Louvain, Brussels, Belgium

Background Beta-lactams are known to be substrates of the OAT and PEPT transporters in eucaryotic cells. MF express MRP and P-gp transporters which may recognize anionic and cationic drugs respectively. We have examined whether AMPI (zwitterion) and two of its cationic ester prodrugs (pivaloylester [PIVA] and phthalimidomethylester [PIMA], which accumulate in MF [Chanteux et al, 41[st] ICAAC, 2070]), could be substrates of MRP and P-gp. Methods We have assesssed the influence of inhibitors of MRP (probenecid [PB;5mM], gemfibrozil [GZ; 200microM]) and P-gp (Cyclosporin A [CyA; 50 microM], GF120918 [GF; 200nM]) on the accumulation of AMPI, PIVA and PIMA in MF . Ciprofloxacin [CIP] and azithromycin [AZ], substrates of MRP and P-gp, respectively, were examined in parallel. Results Additional studies showed that an increase in the extracellular concentration was without effect on AMPI accumulation ratio, and decreased those of PIVA and PIMA. Conversely, CIP and AZ showed higher Cc/Ce at larger concentrations (due to drug-dependent saturation of the corresponding efflux transporters). Conclusion: Neither AMPI nor its ester prodrugs PIVA or PIMA are substrate of MRP or P-gp in J774 MF .

Publication Types:

• Meeting Abstracts

Keywords:

• 2-amino-1-methyl-5-propylideneimidazol-4-one
• Acridines
• Ampicillin
• Azithromycin
• Ciprofloxacin
• Esters
• GF 120918
• Imidazoles
• Macrophages
• Multidrug Resistance-Associated Proteins
• Probenecid
• Prodrugs
• Tetrahydroisoquinolines
• cdc42 GTP-Binding Protein

Other ID:

• GWAIDS0027600

UI: 102267224

From Meeting Abstracts