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Pharmacology

Influences of Urinary pH on Ciprofloxacin Pharmacokinetics in Humans and Antimicrobial Activity In Vitro versus Those of Sparfloxacin

Marika Kamberi, Kimiko Tsutsumi, Tsutomu Kotegawa, Koichi Kawano, Koichi Nakamura, Yoshihito Niki, Shigeyuki Nakano
Marika Kamberi
Department of Clinical Pharmacology and Therapeutics, Oita Medical University, Oita,
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Kimiko Tsutsumi
Department of Clinical Pharmacology and Therapeutics, Oita Medical University, Oita,
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Tsutomu Kotegawa
Department of Clinical Pharmacology and Therapeutics, Oita Medical University, Oita,
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Koichi Kawano
Bayer Yakuhin Ltd., Osaka, and
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Koichi Nakamura
Department of Clinical Pharmacology and Therapeutics, Oita Medical University, Oita,
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Yoshihito Niki
Division of Respiratory Diseases, Department of Medicine, Kawasaki School of Medicine, Kawasaki, Japan
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Shigeyuki Nakano
Department of Clinical Pharmacology and Therapeutics, Oita Medical University, Oita,
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DOI: 10.1128/AAC.43.3.525
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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 asEscherichia 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 againstE. 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.

  • Copyright © 1999 American Society for Microbiology
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Influences of Urinary pH on Ciprofloxacin Pharmacokinetics in Humans and Antimicrobial Activity In Vitro versus Those of Sparfloxacin
Marika Kamberi, Kimiko Tsutsumi, Tsutomu Kotegawa, Koichi Kawano, Koichi Nakamura, Yoshihito Niki, Shigeyuki Nakano
Antimicrobial Agents and Chemotherapy Mar 1999, 43 (3) 525-529; DOI: 10.1128/AAC.43.3.525

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Influences of Urinary pH on Ciprofloxacin Pharmacokinetics in Humans and Antimicrobial Activity In Vitro versus Those of Sparfloxacin
Marika Kamberi, Kimiko Tsutsumi, Tsutomu Kotegawa, Koichi Kawano, Koichi Nakamura, Yoshihito Niki, Shigeyuki Nakano
Antimicrobial Agents and Chemotherapy Mar 1999, 43 (3) 525-529; DOI: 10.1128/AAC.43.3.525
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KEYWORDS

anti-infective agents
ciprofloxacin
fluoroquinolones

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