In an open, randomized, six-period crossover study, the pharmacokinetics of ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin were compared after a single oral dose in 12 healthy volunteers (6 men and 6 women). The volunteers received 250 mg of ciprofloxacin, 400 mg of gatifloxacin, 600 mg of grepafloxacin, 500 mg of levofloxacin, 400 mg of moxifloxacin, and 200 mg of trovafloxacin. The concentrations of the six fluoroquinolones in serum and urine were measured by a validated high-performance liquid chromatography method. Blood and urine samples were collected before and at different time points up to 48 h after medication. Levofloxacin had the highest peak concentration (C max , in micrograms per milliliter) (6.21 ؎ 1.34), followed by moxifloxacin (4.34 ؎ 1.61) and gatifloxacin (3.42 ؎ 0.74). Elimination half-lives ranged from 12.12 ؎ 3.93 h (grepafloxacin) to 5.37 ؎ 0.82 h (ciprofloxacin). The total areas under the curve (AUC tot , in microgram-hours per milliliter) for levofloxacin (44.8 ؎ 4.4), moxifloxacin (39.3 ؎ 5.35), and gatifloxacin (30 ؎ 3.8) were significantly higher than that for ciprofloxacin (5.75 ؎ 1.25). Calculated from a normalized dose of 200 mg, the highest C max s (in micrograms per milliliter) were observed for levofloxacin (2.48 ؎ 0.53), followed by moxifloxacin (2.17 ؎ 0.81) and trovafloxacin (2.09 ؎ 0.58). The highest AUC tot (in microgram-hours per milliliter) for a 200-mg dose were observed for moxifloxacin (19.7 ؎ 2.67) and trovafloxacin (19.5 ؎ 3.1); the lowest was observed for ciprofloxacin (4.6 ؎ 1.0). No serious adverse event was observed during the study period. The five recently developed fluoroquinolones (gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, and trovafloxacin) showed greater bioavailability, longer half-lives, and higher C max s than ciprofloxacin.Fluoroquinolones are widely used alternatives to ␤-lactam agents in the treatment of many bacterial infections. Their antimicrobial activity results from a selective antagonism between host DNA and bacterial DNA without interfering with eucaryotic topoisomerases. The early fluoroquinolones, from the early 1960s, had a limited spectrum of antibacterial activity, mainly against gram-negative pathogens. Further observations of structure-related increases in activity, changes in pharmacokinetic characteristics, and reduced toxicity were followed by numerous chemical modifications of the quinolone molecule. The resulting new fluoroquinolone antimicrobial agents have enhanced activity against gram-positive organisms and anaerobes (1, 2) and improved pharmacokinetic parameters in comparison to previous derivatives. However, only reports on single-drug kinetics have been published so far, and there have been no direct comparisons between the new drugs and the standard drug, ciprofloxacin (1-3).We therefore evaluated and compared the pharmacokinetics of six fluoroquinolones after a single oral dose in the same volunteers.( (mean, 28.4 Ϯ 4.3 years) and with an average weight of 67.4 ...

Stage melanoma IV has a poor prognosis, with a median survival time between 3 and 11 months from the diagnosis of distant metastases. Response rates in first-line regimens are around 20%. To date, no second-line treatment has been established. We performed a randomized, multicentre, second-line clinical phase II study of paclitaxel either as monotherapy or combined with carboplatin given on an outpatient basis. In arm A, paclitaxel was administered at a dose of 100 mg/m2 intravenously on day 1 each week for 6 weeks. In arm B, paclitaxel was administered at a dose of 80 mg/m2 intravenously followed by carboplatin 200 mg/m2 on day 1 each week for 6 weeks. The next cycle was administered after a 2 week intermission. The response rate, survival time, time-to-progression and toxicity were assessed in both arms. The study was stopped after 40 patients because the overall response rate was below 10% in both arms. The median survival time after initiation of second-line treatment was 209 days (+/- 196 days) for patients treated with paclitaxel only, and 218 days for those treated with paclitaxel/carboplatin. The median time-to-progression was around 56 days in both arms. Two partial responses were observed after 16 weeks, lasting for 8 and 12 weeks, respectively. Although both treatment modalities were well tolerated, haematological toxicity was higher in the combination arm. This is so far the largest second-line clinical phase II study reported in melanoma. However, paclitaxel with or without carboplatin had only limited efficacy, and the combination of these drugs adds significantly to haematological toxicity without improving response or survival rates.