Distribution of ciprofloxacin in ascitic fluid following administration of a single oral dose of 750 milligrams

Abstract

The penetration of ciprofloxacin into the ascitic fluid of eight patients was studied. Serum and ascitic fluid samples were obtained before and at 1, 2, 3, 6, and 12 h following administration of a single oral dose of 750 mg. Peak levels (mean ± standard deviation) were 4.0 ± 0.7 ,ug/mi in serum and 2.6 + 0.6 pg/ml in ascitic fluid; the areas under the curve (0 to 12 h) were 29.1 + 6.5 pg -h/ml in serum and 20.7 + 5.0 pg -h/ml in ascitic fluid. The concentrations that were achieved are well above the MICs of ciprofloxacin for the members of the family Enterobacteriaceae that cause spontaneous bacterial peritonitis.Ascitic fluid is a favorable milieu for bacterial proliferation. Consequently, spontaneous bacterial peritonitis is not an uncommon complication in patients with ascites. A variety of pathogens have been implicated, the most common being Escherichia coli and streptococci (7). Despite the increased awareness of the entity and the tendency toward early diagnosis and aggressive antimicrobial therapy, the mortality from spontaneous bacterial peritonitis remains high (6).Ciprofloxacin combines a broad antibacterial spectrum, with particularly good activity against gram-negative organisms, with good intestinal absorption and generally mild adverse effects (1). Such characteristics make it an interesting agent for the treatment of spontaneous bacterial peritonitis. This prompted us to investigate the pharmacokinetics of ciprofloxacin in uninflamed ascitic fluid.Eight patients with ascites secondary to abdominal malignancy (four patients) or advanced heart failure (four patients) were studied. The study was approved by the Hospital Ethical Committee, and informed consent was obtained from all patients. There were four men and four women with a mean (+ standard deviation) age of 65.3 + 15.1 years (range, 42 to 85 years) and a mean body weight of 71.8 + 10.8 kg (range, 62 to 88 kg). None of the patients had received antacids or antimicrobial agents in the preceding 72 h or had clinical evidence of peritonitis.A single dose of 750 mg of ciprofloxacin was administered orally. Blood and ascitic fluid samples were collected via indwelling catheters before drug administration (time zero) and at 1, 2, 3, 6, and 12 h thereafter. Serum was separated from blood by centrifugation, and all samples were stored at -70°C until the time of assay. Ciprofloxacin levels were determined by high-pressure liquid chromatography by the method described by Gau et al. (2). The limit of sensitivity of the method was 0.05 ,ug/ml; the coefficients of variation determined for concentrations of 1 ,ug/ml were 4.1% for intraday variations and 6.3% for interday variations. Samples obtained before drug administration were also tested for alkaline phosphatase, creatinine (serum), cell count, and culture (ascitic fluid).Pharmacokinetic evaluation. The plasma and ascitic fluid concentration-versus-time curves were plotted semilogarith-* Corresponding author. mically for each subject, the beginning of the terminal elimination phase was determined by...

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Η Φαρμακοκινητική Της Σιπροφλοξασίνης Σε Ασθενείς Με Παρόξυνση Χρόνιας Αποφρακτικής Πνευμονοπάθειας Στη Μονάδα Εντατικής Θεραπείας

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