Table 1

Physicochemical and pharmacokinetic parameters of quinolone antibiotics

ParametersUnitsNFLXAM-1155OFLXFLRXSPFXPFLX
Mw1-a 319375361369392333
log Papp b,c −1.34−1.14−0.62−0.76−0.310.06
fu c,d 0.70 ± 0.030.68 ± 0.030.77 ± 0.040.53 ± 0.020.50 ± 0.050.57 ± 0.03
D w 1-e cm2/min4.59 × 10−4 4.37 × 10−4 4.42 × 10−4 4.39 × 10−4 4.31 × 10−4 4.53 × 10−4
D t 1-f cm2/min5.34 × 10−5 4.03 × 10−5 4.08 × 10−5 3.74 × 10−5 3.98 × 10−5 4.08 × 10−5
V br 1-g ml/g brain0.9751.941-h 1.942.721.941-h 2.13
A1-i μg/ml41.057.346.379.463.045.6
B1-i μg/ml9.057.224.709.674.768.33
α1-i min−1 0.9802.903.394.255.594.10
β1-i min−1 0.06330.05450.03030.06760.04970.0754
PSBBB,app d,j μl/min/g brain1.75 ± 0.764.38 ± 2.653.38 ± 0.8317.8 ± 5.249.1 ± 6.161.8 ± 18.8
PSCSF,app d,k μl/min1.23 ± 0.495.15 ± 0.975.98 ± 1.1714.2 ± 3.633.0 ± 4.427.6 ± 4.3
PSCSF,eff 1-l μl/min0.2431.053.052.172.734.81
CLCSF 1-m μl/min13.6 ± 3.622.3 ± 2.219.5 ± 2.220.5 ± 2.446.6 ± 8.134.5 ± 3.5
K p,u,br c,d,n ml/g brain0.0111 ± 0.00660.106 ± 0.0140.173 ± 0.0120.288 ± 0.0570.238 ± 0.0230.254 ± 0.026
K p,u,CSF c,d 0.0475 ± 0.0050.134 ± 0.0010.199 ± 0.0110.378 ± 0.0190.282 ± 0.0270.355 ± 0.009
  • 1-a Molecular weight.

  • 1-b Apparent partition coefficient between 1-octanol and pH 7.4 buffer.

  • 1-c Obtained from a previous report (Ooie et al., 1996c).

  • 1-d Values represent the means ± S.E.

  • 1-e Estimated from the Mw using the relationship reported previously (Fenstermacher and Kaye, 1988).

  • 1-f Estimated from Dw using theVbr value based on a previous report (Fenstermacher and Kaye, 1988).

  • 1-g Values, except for AM-1155 and SPFX, were obtained from a previous report (Ooie et al., 1997).

  • 1-h Obtained from the mean value of NFLX, OFLX, FLRX and PFLX reported previously (Ooie et al., 1997).

  • 1-i Obtained from the observed values in figure 2A by nonlinear least squares regression analysis by equation: Embedded Image

  • 1-j Apparent BBB permeability clearance was obtained from theCbr/AUCu 1 min after i.v. bolus administration.

  • 1-k Apparent BCSFB permeability clearance was obtained from theCCSF/AUCu 1 min after i.v. bolus administration.

  • 1-l Obtained from a previous report (Ooie et al., 1996a).

  • 1-m Estimated from the CSF concentration-time profile reported previously (Ooie et al., 1996b) by nonlinear least squares regression analysis. Values are expressed as the mean ± calculated S.D.

  • 1-n Obtained from reported value by subtracting the vascular volume of brain capillary lumen.