The pharmacokinetics of ciprofloxacin was studied in 12 volunteers during a 5-day course of 500 mg of ciprofloxacin given orally twice a day. The effects on the microflora of saliva and feces were also examined. Serum and urine samples were assayed for ciprofloxacin microbiologically, and the salivary and fecal microflora were examined quantitatively after processing onto a series of selective media. Fecal samples were also investigated for the presence of Clostridium difficile and its cytotoxin. The MICs for new colonizing bacteria were examined in the salivary and fecal samples. There was no accumulation during the course of 5 days with peak serum concentrations identical (2.8 and 2.3 mg/liter) after the first and final doses, and the areas under the serum curves were similar (9.6 mg/liter). The serum half-life was 2.5 h on both days. The changes in the salivary flora were minor and affected only the neisseriae. In the fecal flora, the numbers of enterobacteria and enterococci decreased markedly, whereas the changes in anaerobic flora (anaerobic cocci, fusobacteria, and bacteroids) were not so pronounced. However, 14 days after the drug was discontinued, the salivary and fecal flora were normalized in all respects. No new colonization of ciprofloxacin-resistant bacteria for which MICs were above 1.0 mg/liter was observed. C. difficile or its cytotoxin was not detected.Ciprofloxacin, a new antibacterial agent belonging to the series of 4-quinolone carboxylic acids, is chemically related to the less antibacterially active nalidixic acid, norfloxacin, and ofloxacin (6,11,15). Ciprofloxacin is highly active, with MICs mostly below 0.25 mg/liter for gram-negative aerobic rods (e.g., enterobacteria, including Serratia spp. and Enterobacter spp., and Haemophilus spp.) and oxidative rods (including Pseudomonas aeruginosa) and below 2 mg/liter for most gram-positive aerobic cocci. The substance is generally less active against anaerobic bacteria (11), and the MIC for Clostridium difficile is between 4 and 8 mg/liter (1).The present investigation was carried out to study the pharmacokinetics of ciprofloxacin in healthy volunteers, both men and women, during repeated dosing for 5 days and to assess the effects on the oropharyngeal and colonic microflora. MATERIALS AND METHODSVolunteers. Participating in the study were 12 healthy volunteers, six women and six men. They had a mean weight of 68.0 + (standard deviation) 10.6 kg (range, 54 to 85 kg) and were 26.0 + 2.6 (range, 21 to 30) years old.

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The pharmacokinetics of ciprofloxacin were evaluated after increasing single oral doses of 100, 250, 500 and 1000 mg, and an intravenous dose of 100 mg given to each of 12 healthy volunteers (6 females and 6 males). Concentrations in serum and urine were determined by microbiological assay. The rise in peak serum concentrations and the values of the total area under the serum concentration curve were proportional to the increase in the oral doses. As the oral dose increased a slight increase was observed in the apparent time lag before absorption from 0.34 h after 100 mg to 0.53 h after 1000 mg. The serum half-life after the intravenous dose was 3.2 h. After the oral doses shorter apparent half-life values were observed. The intravenous dose showed an elimination phase distribution volume of 2.76 l/kg and total body clearance of 40.7 l/h. The total urinary excretion was 42.2 +/- 15.6% of the dose after the intravenous dose; the figure was lower after the oral doses. The bioavailability of the 100 mg oral dose was 83.7% as calculated from the value of the total area under the serum curve after the same oral and intravenous dose in all 12 subjects. Ciprofloxacin thus demonstrates normal linear pharmacokinetics, the rise in serum concentrations being proportional to the dose.