STRUCTURE-ABSORPTION RELATIONSHIPS OF A SERIES OF 6-FLUOROQUINOLONES

The physicochemical constants and some structural parameters (topologi cal, steric, and electronic) of eight third-generation monofluorate qu inolones (six uncommercialized and two used clinically [ciprofloxacin and enrofloxacin]) were determined: pK(a), intrinsic solubility (S-O), chromatographic capacity factor, partition coefficient (P), valency m olecular connectivity, molecular volume, molecular surface area, dipol ar moment, and charges associated with each atom of the molecule. The apparent intestinal absorption rate constants (K-abs) in rat (in vivo perfusion) and the MICs at which 90% of the isolates are inhibited (MI C(90)s) against 100 Escherichia coli strains were also determined. We sought to establish simple nonlinear and multiple linear correlations between K-abs, on the one hand, and lipophilic parameters and other ph ysicochemical and structural parameters estimated. Of the nonlinear fu nctions examined, the hyperbolic had the best correlation between K-ab s and P, which was in accordance with the Wagner-Sedman (J. G. Wagner and A. J. Sedman, J. Pharmacokinet. Biopharm. 1:23-50, 1973) equation, whereas, after application of the stepwise multiple linear regression method, a multiple linear correlation with some predictive value coul d be established only between K-abs as a dependent variable and log P and log S-O as independent variables. In conclusion, the K-abs and MIC 90 of the quinolone CNV 8902 suggest that it is a sufficiently interes ting compound to warrant the investigation of its potential therapeuti c use orally.