Structure-absorption relationships of a series of 6-fluoroquinolones

Abstract

The physicochemical constants and some structural parameters (topological, steric, and electronic) of eight third-generation monofluorate quinolones (six uncommercialized and two used clinically [ciprofloxacin and enrofloxacin]) were determined: pKa, intrinsic solubility (S0), chromatographic capacity factor, partition coefficient (P), valency molecular connectivity, molecular volume, molecular surface area, dipolar 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 (MIC90s) 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 physicochemical and structural parameters estimated. Of the nonlinear functions examined, the hyperbolic had the best correlation between K(abs) 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 could be established only between K(abs) as a dependent variable and log P and log S0 as independent variables. In conclusion, the K(abs) and MIC90 of the quinolone CNV 8902 suggest that it is a sufficiently interesting compound to warrant the investigation of its potential therapeutic use orally.

Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Ciprofloxacin Hydrochloride

“…At 378C, values of pK a1 and pK a2 are 6.2 and 8.59, respectively, have been reported. 14 At 258C, pK a values of 6.8 and 8. 73-8.76 were reported.…”

“…The n-octanol/pH 7.0 buffered solution partition coefficient (log P) of ciprofloxacin was reported as À0.94 at 378C, 16 À1.45 (temperature not given) 14 and À1.70 at 258C and pH 7.2. 17 Similarly, calculations using fragmentation methods based on atomic contributions to lipophilicity employing the C log P 1 gave values of À1.15 for C log P and 1.32 for log P. These values are lower than the corresponding values of 1.35 (C log P) and 1.72 (log P) for the highly permeable marker drug metoprolol.…”

Antibacterial evaluation of a collection of norfloxacin and ciprofloxacin derivatives against multiresistant bacteria

“…In addition, 30 A. baumannii and 31 S. maltophilia clinical isolates were used to test the compound with the best activity. Ciprofloxacin, norfloxacin and their derivatives were synthesised as described previously [14,15] and were provided by Cenavisa, S.A. Laboratories (Reus, Spain). Antimicrobial susceptibility was determined by the broth microdilution method according to National Committee for Clinical Laboratory Standards guidelines [16].…”

Poly (vinyl alcohol)/chitosan cryogels as PH responsive ciprofloxacin carriers

“…Ciprofloxacin is a zwitterionic molecule containing two proton-binding sites. At 37°C, its pK a1 and pK a2 are 6.2 and 8.59 [39]. It is known that CF has a pH depended solubility.…”