Interactions between quinolone antibiotics and phospholipid membrane for prediction of alveolar macrophage uptake in vitro

AIM: To compare the effectiveness of the different parameters for predicting alveolar macrophage (AM) uptake, interactions between quinolones, including two amphipathic bases, and phospholipid membrane were evaluated by three different membrane-like systems. METHODS: AM cells were isolated, cultured as confluent monolayers, then incubated with drug solution at 37°C. At designated time points, uptake was terminated by aspirating solution, followed by rinsing, cell lysis, and analysis of drug and protein concentrations. Immobilized artificial membrane (IAM) chromatography and liposome/buffer system were used to determine interactions with phospholipid membrane, expressed as lipophilicity indices, lg k_IAM and lg D_L/B,7.4, respectively. An n-octanol/buffer system was also employed as the reference hydrophobicity, lg D_O/B,7.4. RESULTS: For the tested set, lg k_IAM correlated more significantly with lg D_L/B,7.4 (r² = 0.93) than with lgD_O/B,7.4 (r² = 0.65). There were better correlations between either lg k_IAM or lg D_L/B,7.4 and the extent of accumulation in AM than did lg D_O/B,7.4 (r² = 0.89, 0.92, and 0.67, respectively). Correlations obtained using lg k_IAM, lg D_L/B,7.4, and lg D_O/B,7.4 were comparable when regressed against the logarithm of influx rate into AM for a set consisting of five amphoteric quinolones and quinidine. CONCLUSION: Liposome/buffer system and IAM chromatography could provide nearly similar scale of lipophilicity measurement, both distinct from n-octanol/buffer system. Accumulation by AM was better described by lg k_IAM or lg D_L/B,7.4 than lg D_O/B,7.4, and the passive diffusion was principal form during drugs transported across AM membrane.