Twelve male subjects, aged 19 to 40 years, shown to be healthy by examination and laboratory tests, took 500 mg of ciprofloxacin every 12 h for 7 days. After the first and the last dose, blood and urine samples were taken and drug concentrations were determined by bioassay. There was a significant buildup in mean concentrations in serum from day 1 to day 7; mean peak levels (attained after 1 to 2 h) were 1.9 and 2.8 ,ug/ml, respectively. The terminal half-life was 3.5 to 4 h. About 40% of the drug was excreted into the urine during the 12-h period after dosing; minimum mean concentrations in urine were 105 ,ug/ml on day 1 and 174 ,ug/ml on day 7. Considerable amounts of ciprofloxacin were found in the feces on day 7 (185 to 2,220 ,Lg/g). Marked changes in the aerobic part of the fecal flora were observed as a result of taking ciprofloxacin: coliforms were absent on day 7, and concentrations of streptococci and staphylococci were significantly reduced. There was no overgrowth by yeasts. One week later the fecal flora had returned to a state similar to that found before treatment. Anaerobes were little affected quantitatively but acquired resistance to ciprofloxacin. Side effects were mild and transient.

A 7-day course of either cephradine or amoxicillin-clavulanate treatment caused no significant change in fecal flora composition, except that staphylococci were virtually eliminated in both groups. Some amoxicillin-resistant coliforms were isolated after treatment in both groups, but cephradine- or amoxicillin-clavulanate-resistant coliforms were rarely isolated.

Three different intramuscular formulations of cefonicid (a new long acting cephalosporin) have been tested for bioavailability in 12 healthy volunteers, using a triple crossover design. No significant differences were detectable between the bioequivalence of the three formulations in terms of area-under-curve and 24-h urinary excretion. However, one of the formulations (A) was absorbed significantly more rapidly from the site of injection, causing higher serum levels for up to 1.5 h after administration. A significantly greater urinary excretion was also found up to 8 h after administration of formulation A. All three formulations were well tolerated, and no side-effects or significant changes in laboratory tests were observed.