ABSTRACT
14C-Nitroxoline was given orally to the rats, and its distribution as well as plasma and bile levels were determined autoradiographically and by the aid of radioactivity measurements, respectively. Nitroxoline was also given to the human volunteers orally and intravenously in three various doses and the corresponding urine concentrations of unconjugated and conjugated nitroxoline were determined spectrophotometrically. A pharmacokinetical model was generated on the basis of the results. The curve fitting procedure between total nitroxoline cumulative quantities in urine and the model response simulated on analog-hybrid computer enabled the evaluation of the validity of the chosen model as well as of the identification of its parameters.
Subject(s)
Anti-Infective Agents, Urinary/metabolism , Nitroquinolines/metabolism , Adult , Animals , Anti-Infective Agents, Urinary/blood , Anti-Infective Agents, Urinary/urine , Autoradiography , Bile/metabolism , Humans , Kinetics , Male , Models, Biological , Nitroquinolines/blood , Nitroquinolines/urine , Oxyquinoline/analogs & derivatives , Oxyquinoline/blood , Oxyquinoline/metabolism , Oxyquinoline/urine , Rats , Time FactorsABSTRACT
In vitro studies on the antibacterial activity of nitroxoline and sulphamethizole, alone and in combination, were undertaken and minimal inhibitory concentrations (MICs) determined on a range of urinary pathogens. Eighty per cent of the strains tested were sensitive to less than or equal to 16 mg/l of nitroxoline, and all strains, including Pseudomonas aeruginosa and Streptococcus faecalis, were sensitive to less than or equal to 64 mg/l of nitroxoline. No synergism could be demonstrated with sulphamethizole, but the combination was antagonistic when tested against strains of Ps. aeruginosa and Strep. faecalis. An in vivo study on 10 volunteers showed excellent urinary levels of nitroxoline and sulphamethizole after an oral dose of 160 mg of each agent, and 6-hour urinary nitroxoline levels were greater than or equal to 64 mg/l in 9 of the 10 subjects, and sulphamethizole levels were greater than or equal to 64 mg/l in all 10 subjects. Laboratory findings suggest that nitroxoline and sulphamethizole are both suitable agents for use in urinary tract infections caused by organisms sensitive to these agents, but there appears to be litte advantage in using them in combination.
