This study was designed to determine the effects of an aluminum hydroxide antacid and a calcium carbonate antacid on the bioavailability of ciprofloxacin (Cipro). Cipro (750 mg) was administered orally to 12 healthy volunteers in a three-way randomized crossover design. The three treatments included Cipro alone, four 850-mg calcium carbonate tablets taken 5 min before Cipro, and three 600-mg aluminum hydroxide tablets taken 5 min before Cipro. The relative bioavailability of Cipro when given with calcium carbonate was approximately 60%o of the control value. When Cipro was given with aluminum hydroxide, the relative bioavailability was approximately 15%. Urinary recovery of Cipro in the aluminum hydroxide treatment group was approximately one-fourth of that in the calcium carbonate group. Although calcium carbonate decreased absorption to a lesser extent than aluminum hydroxide, these data suggest that antacids containing either aluminum or calcium should not be given concomitantly with Cipro.Ciprofloxacin is a widely used antimicrobial agent belonging to the quinolone class. As has been previously demonstrated both in healthy volunteers (5) and in elderly patients (8), absorption of ciprofloxacin is decreased by concomitant administration of antacids which contain both aluminum and magnesium. Recently it was shown that the extent of this interaction with the antacid Maalox decreases as the time interval between antacid administration and ciprofloxacin dosing increases (7). Fleming and coworkers observed that Titralac, an antacid that contains only calcium, did not inhibit ciprofloxacin absorption in chronic ambulatory peritoneal dialysis patients (2). Golper et al. (4) observed that in three patients taking aluminum hydroxide, the peak concentration of ciprofloxacin was decreased. Thus, we decided to confirm the observations of Fleming and Golper in a wellcontrolled crossover design study. Therefore, the two objectives of this study were to investigate the effect of concomitant administration of aluminum hydroxide (Amphojel) doses were chosen to approximate the acid-neutralizing capacity of a 30-ml dose of Maalox so that this study could be compared to prior research. In each treatment, the volunteers also consumed 180 ml of water. The subjects consumed a standardized meal 4 h after ciprofloxacin dosing. Blood samples were collected into nonheparinized tubes by direct venipuncture immediately before each dose and at 0.33, 0.67, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 h after dosing. The serum was separated and frozen at -20°C until it could be analyzed. In addition, urine was collected at the following intervals: 0 to 2, 2 to 4, 4 to 8, 8 to 12, and 12 to 24 h after ciprofloxacin dosing. The total volume was recorded, and an aliquot was frozen for future analysis. The serum and urine samples were assayed for ciprofloxacin by using a highperformance liquid chromatographic method developed by Krol and coworkers (6). The isopropyl analog of ciprofloxacin was used as an internal standard. The urine samples were chr...

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Healthy subjects were given single intravenous doses of ciprofloxacin, azlocilin, and the two drugs simultaneously on separate occasions. High-pressure liquid chromatographic analysis was used to assay the concentrations of both drugs in serum and urine. Pharmacokinetic parameters were calculated by noncompartmental methods. The total body (CL), renal (CLR), and nonrenal (CLNR) clearances; steady-state volume of distribution (V.); and fractional urinary excretion of ciprofloxacin were all markedly decreased with the simultaneous administration of azlocillin. The disposition of azlocillin was unchanged when it was given with ciprofloxacin compared to when it was given alone. The pharmacokinetic parameters (mean ± standard deviation) of ciprofloxacin given alone versus in combination with azlocillin were as follows: CL, 52.2 ± 9.2 versus 33.9 ± 6.0 liters/h (P < 0.0005); CLR, 26.5 _ 4.8 versus 16.2 ± 4.2 liters/h (P < 0.0005); CLNR, 25.8 ± 5.5 versus 17.7 ± 4.0 liters/h (P < 0.03); V., 224 ± 30 versus 166 ± 41 liters (P < 0.01); fractional urinary excretion, 0.56 ± 0.06 versus 0.43 ± 0.04 (P < 0.002), respectively. This interaction resulted in significantly higher and more prolonged concentrations of ciprofloxacin in serum, which may be beneficial in the treatment of serious gram-negative bacterial infections, but it could also produce greater toxicity or result in more pronounced effects on oxidative drug metabolism of other medications.Ciprofloxacin, a fluorinated quinolone, and azlocillin, a ureidopenicillin, may potentially be used in combination for the treatment of gram-negative bacterial infections (3). It has been demonstrated, in experimental models of infection, that azlocillin can prevent the emergence of ciprofloxacin-resistant mutants of Pseudomonas aeruginosa (11). Additionally, the drugs in combination may exert a synergistic effect against selected organisms such as P. aeruginosa (1).Both ciprofloxacin and azlocillin are eliminated by the renal (tubular secretion, glomerular filtration) and hepatic (biliary excretion, metabolism) routes (2, 7, 10). Both are organic acids and, therefore, may compete for elimination if they are given together. This would potentially increase and prolong the concentrations of one or both drugs in serum.Thus, the purpose of this study was to determine whether the simultaneous administration of parenteral ciprofloxacin and azlocillin results in altered elimination of either or both drugs. MATERLALS AND METHODSDosage regimens and subjects. Six healthy male volunteers (age, 22 + 3 years; weight, 77 ± 13 kg) received single doses of ciprofloxacin (4 mg/kg intravenously), azlocillin (60 mg/kg intravenously) and the two drugs simultaneously on three separate occasions separated by at least 1 week. Both drugs were diluted to a final volume of 50 ml in suitable vehicles and administered as a constant-rate infusion with a syringe pump over 30 min. Informed consent was obtained from each subject before his participation in the study, and the experimental protocol was approved by...