Raltegravir is a novel human immunodeficiency virus-1 integrase inhibitor with potent in vitro activity (95% inhibitory concentration (IC95)=33 nM in 50% human serum). Three double-blind, randomized, placebo-controlled, pharmacokinetic, safety, and tolerability studies were conducted: (1) single-dose escalation study (10-1,600 mg), (2) multiple-dose escalation study (100-800 mg q12 h x 10 days), and (3) single-dose female study (400 mg). Raltegravir was rapidly absorbed with a terminal half-life (t1/2) approximately 7-12 h. Approximately 7-14% of raltegravir was excreted unchanged in urine. Area under the curve (AUC)(0-infinity) was similar between male and female subjects. After multiple-dose administration, steady state was achieved within 2 days; there was little to modest accumulation of raltegravir. Trough levels were >33 nM for dose levels of 100 mg and greater. Raltegravir is generally well tolerated at doses of up to 1,600 mg/day given for up to 10 days and exhibits a pharmacokinetic profile supportive of twice-daily dosing with multiple doses of 100 mg and greater achieving trough levels >33 nM.

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...

No abstract

No abstract

No abstract