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...

This study was designed to investigate the expression and functional properties of leukocyte adhesion molecules (LeuCAM; CD11/CD18 family) on human alveolar macrophages (AM) from patients with sarcoidosis and idiopathic pulmonary fibrosis. Cells were obtained by bronchoalveolar lavage (BAL) from 17 patients with sarcoidosis (SA), 15 with idiopathic pulmonary fibrosis (IPF), and 14 nonsmokers (NS). Expression of LeuCAM on freshly isolated cells was studied using the peroxidase-antiperoxidase method with monoclonal antibodies (MoAb) detecting CD11a, CD11b, CD11c, and CD18. The functional properties of the adhesion molecules were studied by measuring superoxide anion production (O2-) of SA and IPF AM after blocking the CD18 molecule by an MoAb. Compared with nonsmokers, the samples from SA and IPF patients contained an increased number of AM expressing CD11a, CD11b, CD11c, and CD18 (all p< 0.008), which was correlated to the number of AM/ml BAL (p < 0.008). Spontaneous O2- secretion of AM was higher in SA (6.4 +/- 1.2 nMO2-/10(6) AM/120 min) and IPF (12.0 +/- 1.1 nMO2-/10(6) AM/120 min) compared with NS (2.5 +/- 0.2 nMO2-/10(6) AM/120 min) (both p < 0.008). Incubation of the AM with the MoAb anti-CD18 reduced the spontaneous O2- release from SA AM by 52 +/- 8% and from IPF AM by 49 +/- 3% but did not influence O2- release from NS AM (92 +/- 4%). Our data indicate that the increased expression of LeuCAM on AM in subjects with SA and IPF seems to be involved in the increased O2- production of these cells in both diseases.

The observed increased expression of ICAM-1 on pulmonary vascular endothelial cells in smokers compared to nonsmokers may be involved in the increased recruitment of inflammatory cells to the alveolar space of smokers.

The pharmacokinetics of gatifloxacin (400 mg orally) and the influence of the antacid aluminum magnesium hydroxide (20 ml of Maalox 70) on the bioavailability of gatifloxacin in 24 healthy volunteers were assessed. In an open, randomized, six-period crossover study, the volunteers received either gatifloxacin alone (treatments A and D); aluminum magnesium hydroxide concomitant with gatifloxacin (treatment C); or aluminum magnesium hydroxide 2 h before (treatment B), 2 h after (treatment E), or 4 h after gatifloxacin administration (treatment F). Gatifloxacin concentrations were measured by a validated bioassay and high-performance liquid chromatography. Pharmacokinetics of a single 400-mg dose of gatifloxacin alone were characterized as follows (mean ± standard deviation): peak concentration (C max), 3.8 ± 0.5 (treatment A) and 3.4 ± 0.9 (treatment D) μg/ml; time toC max, 1.4 ± 0.8 (treatment A) and 1.7 ± 0.7 (treatment D) h; area under the curve from time zero to infinity (AUC0–∞), 33.5 ± 5.9 (treatment A) and 31.4 ± 3.4 (treatment D) μg · h/ml; urine recovery, (83 ± 6)% (treatment A) and (84 ± 8)% (treatment D). Comparison of the results obtained by bioassay showed a good correlation. Aluminum magnesium hydroxide administration 2 h before (treatment B) or concomitant with (treatment C) gatifloxacin decreased the C max by 45% (2.1 ± 1.2 μg/ml) or even 68% (1.2 ± 0.4 μg/ml) highly significantly (P < 0.01). AUC0–∞ was significantly reduced from 33.5 ± 5.9 to 19.4 ± 6.9 μg · h/ml (by 42%) or even to 11.9 ± 3.3 μg · h/ml (by 64%) (P < 0.01). If aluminum magnesium hydroxide was given 2 h after gatifloxacin (treatment E), there was no significant reduction of concentration in serum but AUC0–∞ was significantly reduced from 31.4 ± 3.4 to 25.9 ± 5.3 μg · h/ml (18%) (P < 0.01). Aluminum magnesium hydroxide given 4 h after gatifloxacin (treatment F) showed no influence on the gatifloxacin pharmacokinetics. Therefore, the optimal time between gatifloxacin application and the intake of an aluminum-containing antacid should be 4 h.