A 500-mg dose of the quinoline ciprofloxacin was administered orally to each of six healthy male volunteers, after which the concentrations of this agent in serum and blister fluid were measured. Absorption appeared to be rapid, with a mean peak level of 2.4 ,ug/ml attained 1.25 h after administration. The serum elimination half-life was 3.9 h. The agent penetrated blister fluid well, the percent penetration being 57%. Urinary recovery of ciprofloxacin was 30%.Ciprofloxacin is a new quinoline carboxylic acid derivative which is well absorbed when administered orally (1, 6). It has high in vitro activity against a broad spectrum of organisms such as Enterobacteriaceae, Pseudomonas aeruginosa, and Bacteroides spp., including strains resistant to aminoglycosides and other commonly used agents such as the broad-spectrum P-lactams. Because of its high activity, it may be possible to use this antimicrobial agent to treat systemic rather than urinary tract infections, as is the case with nalidixic acid and norfloxacin (5).The purpose of this study was to investigate the pharmacokinetic properties of this compound after oral administration and also to determine 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 (7). MATERIALS AND METHODSSix healthy male volunteers were entered into the study; approval was obtained from the Dudley Road Hospital Ethical Committee, and informed consent was gained. They were aged 23 to 41 (mean age, 29 years) with a mean weight of 78 kg (range, 69 to 83 kg). There were no significant episodes in their past medical histories, and their biochemical and hematological profiles were normal. All underwent physical examination the week before the study and all were normal. On the night before the study, two 0.2% cantharidesimpregnated 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. of that evening. At 8 a.m. on the day of the study, they were given a single oral dose of a 500-mg ciprofloxacin tablet with 200 ml of water. Thereafter, fluid was taken ad libitum. Solid food was taken after 2 h.Blood was taken from an indwelling intravenous cannula at 15, 30, 45, 60, and 90 min and 2, 3, 4, 5, 6, 8, and 12 h after the administration of the drug. Urine samples were collected over 0 to 4, 4 to 8, 8 to 12, and 12 to 24 h after administration. The two blisters were sampled at 30 and 60 min and then hourly by using a fine needle. The integrity of the blisters was maintained by spraying with a fast-drying plastic dressing. Approximately 20-,ul samples were used to impregnate preweighed sterile 6-mm assay disks, which were then reweighed to accurately measure the quantity of fluid obtained.The antibiotic assays were performed within 1 h of sample collection, using a plate diffusion assay; the test organism was Escherichia coli 4004 (obtained from Bayer AG, Wupperlal, West Germany). The medium used was IsoSensitest, pH 7...

First-pass metabolism by the intestinal wall is extensive and contributes to the same extent as the liver to low bioavailability of some drugs such as verapamil. Moreover, intestinal secretion is as important as biliary excretion for the elimination of metabolites.