The pharmacokinetics of ertapenem and ceftriaxone were investigated in an open, randomized, two-period crossover study after single-and multiple-dose administration in 10 healthy volunteers (five women and five men). Both antibiotics were administered intravenously once daily for 7 days at dosages of 1 g (ertapenem) and 2 g (ceftriaxone). The concentrations of the antibiotics in serum and urine were quantified by the agar well diffusion method bioassay and, in addition, for ertapenem only, by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). For ertapenem the maximum concentration of the drug in plasma (C max ) was 256 mg/liter, the half-life was 20.7 h, and the area under the plasma concentration-time curve (AUC) was 830 mg ⅐ h/ liter. The concentrations in fecal samples were (mean value) 37.2 and 32.7 mg/kg on day 4 and day 8, respectively. Ceftriaxone exhibited a mean C max of 315 mg/liter, a half-life of 7.6 h, and an AUC of 1,556 mg ⅐ h/liter. The mean concentrations in fecal samples were 153 and 258 mg/kg on day 4 and day 8, respectively. No accumulation of ertapenem or ceftriaxone was detected at steady state. A slightly but significantly decreased AUC for ertapenem was detected for the female volunteers. No serious adverse event was observed. Both antibiotics induced a marked decrease in the anaerobic microflora (4-log-unit decreases in lactobacilli, bifidobacteria, clostridia, and bacteroides) and Escherichia coli, whereas the number of enterococci increased (4 log units). A slight overgrowth of yeasts was observed with both regimens. In all cases the microflora returned to normal levels on days 21 to 35.Ertapenem, recently described as the first class 1 carbapenem (11), is a parenteral broad-spectrum beta-1-methyl-carbapenem with a long half-life in serum. It has been shown to be effective for the treatment of community-acquired pneumonia (9); intra-abdominal infections, skin and skin structure infections, and acute pelvic infections (14); and urinary tract infections (15). In contrast to imipenem and meropenem, ertapenem lacks sufficient activity against Pseudomonas aeruginosa, enterococci, and Acinetobacter spp.; but clinical trials have shown that Pseudomonas infections can be treated with ertapenem.Ertapenem can be administered once daily due to its long half-life in plasma. The long half-life in plasma reflects its high level of plasma protein binding.Ceftriaxone matches ertapenem in both its pharmacokinetics and its antibacterial spectrum for the treatment of community-acquired pneumonia and has been used as a comparator drug for ertapenem in clinical trials (9, 17). Ceftriaxone is a broad-spectrum parenteral cephalosporin with a long half-life that also requires administration only once daily.The application of antibacterial agents for the treatment of infections may have a number of potentially adverse effects on the normal oropharyngeal and intestinal microflora. The normal microflora acts as a barrier against colonization by potentially pathogenic microorganisms and agai...