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  • Title: Influences of urinary pH on ciprofloxacin pharmacokinetics in humans and antimicrobial activity in vitro versus those of sparfloxacin.
    Author: Kamberi M, Tsutsumi K, Kotegawa T, Kawano K, Nakamura K, Niki Y, Nakano S.
    Journal: Antimicrob Agents Chemother; 1999 Mar; 43(3):525-9. PubMed ID: 10049262.
    Abstract:
    The impact of acidification and alkalinization of urine on the pharmacokinetics of ciprofloxacin was investigated after single 200-mg oral doses were administered to nine healthy male volunteers. In addition, the effect of human urine on the MICs of ciprofloxacin and sparfloxacin against some common urinary tract pathogens such as Escherichia coli and Pseudomonas aeruginosa was investigated. Acidic and alkaline conditions were achieved by repeated oral doses of ammonium chloride or sodium bicarbonate, respectively. Plasma ciprofloxacin levels in all subjects were adequately described in terms of two-compartment model kinetics with first-order absorption. Acidification and alkalinization treatments had no effect on ciprofloxacin absorption, distribution, or elimination. The total amount of unchanged ciprofloxacin excreted over 24 h under acidic conditions was 88.4 +/- 14.5 mg (mean +/- standard deviation) (44.2% of the oral dose) and 82.4 +/- 16.5 mg (41.2% of the oral dose) under alkaline conditions, while the total amount of unchanged drug excreted over 24 h in volunteers receiving neither sodium bicarbonate nor ammonium chloride was 90.53 +/- 9.8 mg (45.2% of the oral dose). The mean renal clearance of ciprofloxacin was 16.78 +/- 2.67, 16.08 +/- 3.2, and 16.31 +/- 2.67 liters/h with acidification, alkalinization, and control, respectively. Renal clearance and concentrations of ciprofloxacin in urine were not correlated with urinary pH. The antibacterial activity of ciprofloxacin and sparfloxacin against E. coli NIHJ JC-2 and P. aeruginosa ATCC 27853 was affected by human urine and in particular by its pH. The activities of both quinolones against E. coli NIHJ JC-2 were lower at lower urinary pH and rather uniform, while in the case of P. aeruginosa ATCC 27853 ciprofloxacin was more active than sparfloxacin.
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