Aqueous solubility and distribution of ciprofloxacin, enrofloxacin, norfloxacin and levofloxacin antimicrobials drugs in octanol/buffer system has been measured by the isothermal saturation method using buffer solutions pH 2.0 and 7.4 in the temperature range of 293.15–313.15 K. Thermophysical characteristics for the compounds have been determined by the DSC method. It has been established that the solubility of levofloxacin in these buffers is higher than that of the other fluoroquinolones. HYBOT descriptors for biologically active compounds have been calculated and the impact of the donor-acceptor capacity of the molecules on drugs solubility has been studied. According to the lipophilicity parameter fluoroquinolones are ranged in the following order: enrofloxacin > levofloxacin > ciprofloxacin > norfloxacin. The thermodynamic solubility and distribution functions of the studied compounds have been obtained. The permeability coefficients of the substances through an artificial phospholipid membrane were determined. The drugs with a lower aqueous solubility were estimated to have higher distribution coefficients and membrane permeability.