Original Article

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

Authors: Jin SUN, Yoshiharu DEGUCHI, Ji-Min CHEN, Ru-Hua ZHANG, Kazuhiro MORIMOTO


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 degrees C. At designated time points, uptake was
terminated by aspirating solution, followed by rinsing, cell lysis, a nd 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-octano l/buffer system was also employed as the
reference hydrophobicity, lg D(O/B,7.4)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 DO/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 f or 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.

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