A 100-mg dose of ciprofloxacin was given as an intravenous bolus injection to each of six healthy volunteers, after which the levels of this agent were measured in serum, blister fluid, and urine, After administration, distribution of ciprofloxacin was very rapid, and the mean distribution volume was very large (177 liters). The mean terminal serum half-life was 4.0 h. The agent penetrated blister fluid rapidly, with the mean maximum level being 0.53 ,ug/ml at 30 min, after which time the blister levels exceeded those in serum. The 48-h urinary recovery of ciprofloxacin was about 80%.Ciprofloxacin is a new quinoline carboxylic acid antimicrobial agent which can be given by either the oral or parenteral route (1, 5). It has high in vitro activity against a wide range of pathogens, including members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and grampositive cocci, which includes those strains that are resistant to aminoglycosides and other commonly used agents such as the broad spectrum P-lactam antibiotics.The purpose of this study was to investigate the pharmacokinetic properties of this compound after intravenous administration and to compare the results with those obtained after oral administration (2). The penetration of the agent into chemically induced blister fluid, which has been shown to be similar in composition to the exudate of a mild inflammatory reaction (5), was also investigated. MATERIALS AND METHODSSix healthy male volunteers were entered into the study, five of whom had participated previously in a pharmacokinetic study on oral administration of ciprofloxacin (3). Approval for the study was obtained from the Dudley Road Hospital Ethical Committee, and informed consent was obtained from the volunteers. The ages of the subjects were 23 to 42 years (mean, 29.2 years) with a mean weight of 78.5 kg (range, 65 to 85 Kg) and a mean height of 176.6 cm (range, 169 to 186 cm). There were no significant episodes in their medical history, and biochemical and hematological profiles were normal. All subjects underwent physical examination the week before the study; the results were normal. On the night before the study, two 0.2% cantharides-impregnated plasters (1 by 1 cm) were applied to the volar surface of one forearm and taped in place. The subjects fasted from 10 p.m. the night before the study. At 8 a.m. on the day of the study, the subjects were given an intravenous injection of 100 mg of ciprofloxacin dissolved in 10 ml of distilled water. The subjects drank 200 ml of water in the first 2 h; thereafter, fluid was allowed ad libitum. Solid food was taken after 2 h.Blood was taken from an indwelling intravenous cannula at 5, 10, 15, 30, 45, 60, and 90 min and 2, 3, 4, 5, 6, 7, 8, and 12 h after drug administration. Urine samples were collected over 0 to 4, 4 to 8, 8 to 12, 12 to 24, and 24 to 48 h after administration. On the mornings at 72 and 96 h after drug administration, the first urine specimen of the day was also collected. The two blisters were sampled at 15, 30, and 60 min, hou...

The pharmacokinetics of the quinolone enoxacin were studied after a 600-mg oral dose was given to each of six male volunteers. The levels of the compound were measured in serum, blister fluid, and urine. Absorption was variable, with peak levels (mean, 3.7 ,ug/ml) being attained between 0.75 and 3.0 h (mean, 1.9 h). The serum elimination half-life was 6.2 h, and 71.6% of the drug was recovered in the urine by 48 h. Enoxacin penetrated blister fluid well, the mean percent penetration being 78 Nev., abstr. no. 698, 1983). In general terms, it has a degree of antibacterial activity similar to that of norfloxacin. Enoxacin is absorbed from the gastrointestinal tract, and preliminary studies show that it reaches therapeutic levels in the blood (N. Mertz, T. Chang, J. R. Latts, J. R. Goulet, and G. J. Yakatan, 23rd ICAAC, abstr. no. 858).The purpose of this study was to investigate the pharmacokinetic properties of this compound after oral administration and to determine its penetration into chemically induced blister fluid, which has been shown to be similar in composition to the exudate of a mild inflammatory reaction (11). MATERIALS AND METHODSSix healthy male volunteers were studied after approval had been obtained from Dudley Road Hospital Ethical Committee and written informed consent gained. These volunteers had previously received norfloxacin (1) and ciprofloxacin (4). They were aged 23 to 42 (mean age, 29.5 years); mean weight, 77.3 kg (range, 65 to 85 kg); mean height, 177.0 cm (range, 170 to 185 cm). Their past medical history was without significant episodes, and biochemical and hematological profiles were normal; in particular, tests of liver and renal function were normal. All underwent physical examinations the week before the study and were normal. Before each volunteer went to bed on the night before the study, two 0.2% cantharides-impregnated plasters (1 by 1 cm) were applied to the anterior surface of one forearm and taped in place. The subjects fasted from 10 p.m. on this evening. At 8 a.m. on the day of the study, they were given a single 600-mg oral dose of enoxacin (three tablets of 200 mg) with 300 ml of water. Thereafter, fluid was taken ad libitum. Solid food was taken after 2 h.Blood was drawn through an intravenous cannula kept patent with 1-ml doses of heparin (100 IU/ml) at 0, 15, 30, 45, 60, and 90 min and 2, 3, 4, 5, 6, 8, 12, and 24 h after dosing. Urine samples were collected over 0 to 4, 4 to 8, 8 to 12, 12 to 24, and 24 to 48 h after administration. At approximately 72 and 96 h after administration, the first early-morning specimen of urine was collected. The two blisters were sampled * Corresponding author.with a micropipette at 0, 30, and 60 min and then hourly to 6 h and at 8 and 12 h. The integrity of the blisters was maintained by spraying with a fast-drying plastic dressing. Approximately 25-,ul samples of blister fluid were used to impregnate preweighed, sterile assay disks (6 mm) which were then reweighed to accurately measure the quantity of fluid obtained.The antibiotic ...

Two new quinoline compounds, enoxacin (600 mg) and norfloxacin (400 mg) were administered consecutively to six healthy male volunteers. The levels of the two agents were measured in serum, urine and blister fluid. The mean peak serum level of enoxacin was 3.7 mg/l and attained at a mean time of 1.9 h after administration; the mean peak serum level of norfloxacin was 1.45 mg/l at a mean time of 1.5 h. The mean serum half-lives were 6.2 h for enoxacin and 3.25 h for norfloxacin. Both agents penetrated blister fluid well and reached maximum levels of 2.9 mg/l (for enoxacin) and 1.0 mg/l (for norfloxacin). The 24 h urinary recovery of enoxacin of 61% was about twice that of norfloxacin. No adverse effects of either agent were observed. The data suggest that enoxacin might be used as a once daily dose for the treatment of urinary tract infections, but twice daily for the treatment of susceptible pathogens causing systemic (as against urinary) infections.