Pharmacokinetics and Pharmacodynamics of Intravenous Levofloxacin at 750 Milligrams and Various Doses of Metronidazole in Healthy Adult Subjects
Abstract
The purpose of this investigation was to evaluate the steady-state pharmacokinetics, pharmacodynamics, and safety of intravenous levofloxacin at 750 mg administered once daily combined with three different dosages of intravenous metronidazole (500 mg every 8 h [q8h], 1,000 mg q24h, and 1,500 mg q24h). Eighteen healthy adult subjects received all three combinations in a randomized, crossover fashion. Serial blood and urine samples were collected on the third day of each study period. The 24-h areas under the inhibitory (AUIC(0-24)) and bactericidal (AUBC(0-24)) curves of these three combination regimens were determined against clinical isolates of Bacteroides fragilis, Bacteroides thetaiotaomicron, Peptostreptococcus asaccharolyticus, and Escherichia coli. The mean concentrations of levofloxacin were not different between study periods and were similar to those previously published. The mean (+/- standard deviation) areas under the metronidazole plasma concentration-time curve (AUC(0-24)) for 1,500-mg q24h (338 +/- 105 mg.h/liter) and 500-mg q8h (356 +/- 68 mg.h/liter) regimens were not different (P > 0.05), but both were significantly higher than the 1,000-mg q24h AUC(0-24) (P < 0.05, 227 +/- 57 mg.h/liter). Mean (+/- standard deviation) total body clearance and renal clearance values were similar among the 500-mg q8h, 1,000-mg q24, and 1,500-mg q24h regimens (62 +/- 7, 67 +/- 13, and 67 +/- 14 and 11 +/- 3, 12 +/- 2, and 12 +/- 5 ml/min/1.73 m2, respectively). Levofloxacin…
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Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design.
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