キノロン系抗菌剤の中枢神経内分布：脳からの能動的汲みだし機構の関与

抄録

A distributed model was employed to clarify the mechanism for the restricted distribution of the quinolone antibiotics (norfloxacin, AM-1155, ofloxacin, fleroxacin, sparfloxacin and pefloxacin) in the rat central nervous system (CNS). The permeability-surface area (PS) product for the symmetrical transport across the blood-brain barrier (BBB; PS_{BBB, sym}) and across the blood-cerebrospinal fluid barrier (BCSFB; PS_{BCSFB, sym}), and the efflux clearance across the BBB (PS_{BBB, act}) were obtained by fitting in vivo data to this kinetic model by using a nonlinear least squares regression analysis combined with the fast inverse Laplace transforming program. The values of PS_{BBB, act} were 10- to 260-fold greater than those of PS_{BBB, sym}, providing the kinetic evidence to support the hypothesis that a significant efflux transport at the BBB is responsible for the limited distribution of quinolones in brain tissue. A good correlation between the apparent brain tissue-to-unbound serum concentration ratio at steady-state and the ratio of PS_{BBB, sym} to the sum of PS_{BBB, sym} and PS_{BBB, act} suggests the importance of the efflux transport across the BBB in determining the brain distribution of quinolones.