The effect of antacids on the systemic absorption of oral norfloxacin was evaluated in 12 healthy volunteers. Subjects were given each treatment in a balanced sequence at 7-day intervals. Treatments included 400 mg of norfloxacin alone, 400 mg of norfloxacin 5 min after aluminum-magnesium hydroxide (Maalox), Maalox 2 h after 400 mg of norfloxacin, and 400 mg of norfloxacin 5 min after calcium carbonate (Titralac). Blood and urine samples were collected at predetermined time intervals for 24 and 48 h, respectively. Norfloxacin concentrations in plasma and urine were determined by high-pressure liquid chromatography. The area under the plasma concentration-versus-time curve from time zero to infinity and urinary recovery were used to compare the relative bioavailability of norfloxacin with antacids with that of norfloxacin alone. Norfloxacin bioavailability was markedly reduced when subjects received antacid pretreatment. When norfiloxacin was given 5 min after Maalox and Titralac, the bioavailabilities were 9.02 and 37.5%, respectively, relative to that for 400 mg of norfloxacin alone. When Maalox was given 2 h after norfloxacin, maximal concentrations of norfloxacin in plasma occurred between 1 and 1.5 h postdose, and absorption was reduced to a lesser extent, with a relative bioavailability of 81.31%. Norfloxacin concentrations in urine were also reduced as a result of antacid administration. Antacids containing aluminum and magnesium salts and calcium carbonate should be avoided by patients taking norfloxacin.Norfloxacin is a fluoroquinolone antimicrobial agent that is indicated for treating both complicated and uncomplicated urinary tract infections in patients who are candidates for oral therapy. A prerequisite to using oral antimicrobial agents is assurance that the drug will be absorbed. Antacids containing aluminum and magnesium salts may reduce absorption of the fluoroquinolones (3-6). Chelation between these metal ions and the 3-carboxyl and 4-oxo substituents on the quinolone nucleus results in a complex that is more polar and unable to be absorbed (4). Because this interaction may cause markedly reduced bioavailability, its occurrence may lead to therapeutic failures.In this study, the effects of antacid administration on the systemic bioavailability of oral norfloxacin were evaluated. MATERIALS AND METHODSThe study included 12 males between the ages of 18 and 40 years. Written informed consent was obtained. The subjects were determined to be healthy by physical examination, medical history, electrocardiogram, and laboratory tests. They were free of significant physical or psychological abnormalities, drug abuse, and allergies.A balanced, four-period, crossover design was employed. Subjects received each treatment once, and each treatment period was separated by a 7-day washout period. Treatments included 400 mg of norfloxacin, 400 mg of norfloxacin 5 min after 30 ml of aluminum and magnesium hydroxide (Maalox), 400 mg of norfloxacin followed by 30 ml of Maalox 2 h later, and 400 mg of norfloxacin 5 m...

The effect of gastric acidity on the oral absorption of the quinolone antibiotic enoxacin was evaluated in 12 healthy volunteers. In a randomized, crossover design, single 400 mg oral enoxacin doses were administered on four occasions: alone, after 50 mg intravenous ranitidine, after 2 micrograms/kg subcutaneous pentagastrin, and after combined ranitidine and pentagastrin treatment. Gastric pH was monitored by radiotelemetry capsule for 4 hours after enoxacin administration. Ranitidine pretreatment reduced enoxacin oral bioavailability by an average of 26%. This effect was abolished when pentagastrin was used to maintain low gastric pH. Thus the ranitidine-induced decrease in enoxacin oral bioavailability probably results from a decrease in gastric acidity rather than from an interaction with ranitidine itself.

Intravenous ciprofloxacin in doses ranging from 200 to 400 mg demonstrated linear pharmacokinetics. These single doses were well tolerated, although cases of transient venous irritation and crystalluria were observed.

This study assessed the potential nephrotoxicity of clarithromycin in comparison with gentamicin and placebo. Increased urinary excretion of alanine aminopeptidase (AAP) and N-acetyl-beta-D-glucosaminidase (NAG) served as markers of renal tubular injury. The study utilised a multiple-dose, double-blind, randomised, parallel group design. 14 healthy male subjects received 1 of 3 treatment regimens: (a) clarithromycin 500 mg orally every 12h for 13 doses and intravenous placebo every 8h (n = 5); (b) oral placebo every 12h and intravenous placebo every 8h (n = 4); and (c) intravenous gentamicin 1.7 mg/kg every 8h for 19 doses and oral placebo every 12h (n = 5). 24h urine collections were obtained daily for determinations of AAP and NAG activities. Gentamicin produced statistically significant increases (p less than 0.0001) in AAP and NAG excretion, with increases as early as the first and second day of dosing. Clarithromycin, when compared with placebo, did not produce significant elevations in AAP or NAG activity. On the basis of these data, it is unlikely that usual doses of clarithromycin have significant potential for causing nephrotoxicity.

A study involving 25 healthy male volunteers was conducted to evaluate the effect of lomefloxacin on the pharmacokinetics of theophylline. The mean age was 22.4 + 3.0 years, and the mean weight was 77.3 ± 7.7 kg. A single 6-mg/kg aminophylline dose was given intravenously on study days 1 and 15. The subjects received a 400-mg lomefloxacin dose (four 100-mg capsules) on study days 9 through 15. No treatment was given on study days 2 through 8. Thirteen blood samples were collected within 24 h after each aminophyUline dose. Theophylline concentrations in serum were measured by enzyme immunoassay (EMIT). The mean aminophylline dose was 437 + 36 mg, equivalent to 344 mg of theophylline. Multiple doses of lomefloxacin had no effect on the area under the concentration-time curve from 0 h to infinity, maximal concentration, or clearance of theophylline from serum. There was a slight increase in the theophylline half-life from 6.72 1.63 to 7.02 + 1.37 h after lomefloxacin dosing (P = 0.04); however, the change was clinically insignificant. No change in theophylline dose is required when lomefloxacin therapy is instituted in a patient receiving theophylline.Lomefloxacin is one of several new fluoroquinolone antimicrobial agents and is distinguished by a longer half-life (7.7 h), allowing once-daily dosing (9). Lomefloxacin possesses excellent in vitro activity against Haemophilus influenzae, Branhamella catarrhalis, Klebsiella pneumoniae, and several other organisms associated with purulent bronchitis and pneumonia in patients with obstructive lung disease (4). Thus, theophylline will likely be given with lomefloxacin in some patients.Other fluoroquinolones, including enoxacin and ciprofloxacin, may reduce theophylline clearance by inhibiting metabolism. Enoxacin possesses the most potent metabolic inhibition, resulting in a 41 to 74% reduction in theophylline clearance (2,15,16). Patients receiving enoxacin and theophylline together without compensation for the interaction have suffered nausea, vomiting, seizures, hallucinations, and psychotic reactions (8). Clinically significant elevations in theophylline concentrations in serum associated with severe theophylline toxicity have also been reported with ciprofloxacin treatment (12). Although ofloxacin was associated with a significant decline in theophylline clearance (12%), the magnitude was not clinically significant (6). This study was conducted to determine the effect of lomefloxacin on theophylline elimination. MATERIALS AND METHODSThe study was 0, 0.17, 0.33, 0.5, 0.75, 1, 2, 4, 8, 12, 16, 20, and 24 h relative to the beginning of each theophylline infusion. The blood samples were allowed to clot and were then centrifuged to separate the serum. The serum samples were maintained frozen at -20°C until the theophylline assay.Theophylline in human serum was determined by an enzyme immunoassay (EMIT; Syva Co., Palo Alto, Calif.). The assay precision ranged from 1.40 to 5.2%. The limit of sensitivity was 0.80 ,ug/ml. Concentrations below this value were reported as...