Effect of calcium carbonate on bioavailability of orally administered gemifloxacin

We investigated the effect of calcium carbonate on the oral bioavailability of gemifloxacin. Gemifloxacin was administered alone, 2 h before, simultaneously, or 2 h after calcium carbonate in 16 volunteers. Data for 320 mg of gemifloxacin alone were as follows: maximum concentration of drug in serum (C(max)),13 microg/ml; half-life, 7.33 h; and area under the concentration-time curve from 0 h to infinity (AUC( infinity )), 6.79 microg. h/ml. Only simultaneous coadministration of calcium carbonate reduced C(max) (-17%) and AUC( infinity ) (-21%) significantly.     

Comparative pharmacokinetics of apalcillin and piperacillin

The pharmacokinetics of apalcillin and piperacillin, each administered intravenously as a single 2-g dose, were compared in 10 volunteers in a randomized study of crossover design using bioassay and high-pressure liquid chromatographic procedures. The concentrations of both penicillins in serum were determined over a period of 12 h and in urine over 24 h. Concentrations of apalcillin and piperacillin at the end of the 15-min infusion were similar; however, at 8 h, concentrations of piperacillin were below measurable levels, whereas concentrations of apalcillin were still measurable at 10 h. Pharmacokinetic parameters were calculated according to a two-compartment open model. The area under the curve and the half-life for apalcillin were larger than for piperacillin. On the other hand, renal clearance of piperacillin was substantially greater than that of apalcillin. Of the apalcillin excreted via the kidneys, approximately one-fifth was eliminated as two microbiologically inactive penicilloic acid derivatives. The nonrenal clearance of apalcillin was 79% of total clearance. Binding of apalcillin to serum protein was almost twice that of piperacillin.     

Ertapenem pharmacokinetics and impact on intestinal microflora, in comparison to those of ceftriaxone, after multiple dosing in male and female volunteers

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. 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. 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.     

Pharmacokinetics and serum bactericidal activity of ticarcillin and clavulanic acid

The pharmacokinetics of ticarcillin 5.0 g and clavulanic acid 0.2 g were examined both alone and combined (3.0 or 5.0 g ticarcillin + 0.2 g clavulanic acid as 3.2 or 5.2 g timentin) after a 15 min infusion in ten healthy volunteers. At the same time, the serum bactericidal activity of 5.0 g ticarcillin alone and 5.2 g Timentin was determined against two ticarcillin resistant strains each of Klebsiella oxytoca and Pseudomonas aeruginosa in the first and sixth hour after administration. The serum kinetics of both ticarcillin and clavulanic acid could best be described by an open 2-compartment model. Both substances showed similar kinetic behaviour in serum with a T 1/2 beta of 74.8 +/- 11.5 min for ticarcillin and 76.6 +/- 4.6 min for clavulanic acid. The total clearance of clavulanic acid was 158 +/- 23 ml/min and thus clearly exceeded that of ticarcillin (112 +/- 9 ml/min). The recovery rate in the 24 h urine was 41.3% for clavulanic acid as compared to 79.4% for ticarcillin. Concomitant administration of both substances led to a limited change in the kinetics of both ticarcillin and clavulanic acid. A significant enhancement of the serum bactericidal action of ticarcillin and clavulanic acid was only detected for both Klebsiella species and not for the Ps. aeruginosa species, and only in the first hour.     

Glucocorticoids are not always deleterious for bone

A 23‐year‐old man with the rare sclerosing bone disorder van Buchem disease presented with progressively worsening headaches that eventually became persistent and associated with papilledema. Increased intracranial pressure was diagnosed, and the patient had a ventriculoperitoneal drain inserted as well as simultaneously receiving treatment with prednisone. Before starting treatment, there was biochemical evidence for increased bone turnover and for steady increases in bone mineral density (BMD) at the spine and total hip despite the patient having reached his peak height of 197 cm at the age of 19 years. Treatment with prednisone for 2 years resulted in biochemical and histologic suppression of bone formation as well as of bone resorption and arrest of further bone accumulation. Our data suggest that glucocorticoids (GCs) may represent an attractive alternative to the high‐risk surgical approaches used in the management of patients with progressive sclerosing bone disorders. Our findings also suggest that whereas sclerostin may not be required for the action of GCs on bone formation, it may well be important for the action of GCs on bone resorption. The exact mechanism by which sclerostin may be involved in the regulation of bone resorption is as yet to be explored. © 2010 American Society for Bone and Mineral Research.     

LOX family enzymes expression in vaginal tissue of premenopausal women with severe pelvic organ prolapse

Introduction and Hypothesis  

The extracellular matrix proteins collagen and elastin provide tissue strength and resilience, whereas lysyl oxidase enzymes play a major role in their stabilization. This study examines the expression and tissue localization of lysyl oxidase family proteins in the anterior vaginal wall of premenopausal women with advanced pelvic organ prolapse (POP, n = 15) and asymptomatic controls (n = 11). All women were in the proliferative phase of menstrual cycle.     

Quinolone-induced arthropathy: an update focusing on new mechanistic and clinical data

Quinolones possess favourable antibacterial and pharmacokinetic characteristics and are often used as anti-infective agents in adults. They are contraindicated in children and adolescents because they damage weight-bearing joints in juvenile animals. In addition, they possess a tendotoxic potential. Since ciprofloxacin has been used off-label for decades in children and adolescents, it is known today that no pronounced risks for arthropathies or tendinopathies exist in humans. Recently published clinical studies with gatifloxacin in children support this clinical experience. However, a low risk for joint disorders cannot be excluded and tendinopathies are a generally accepted rare adverse effect of quinolones at least in adults. Isolated case reports of arthralgia in children following quinolone therapy have been published and in studies with levofloxacin the incidence of musculoskeletal disorders was significantly greater in levofloxacin-treated patients than in control patients treated with comparator antibiotics. As a consequence, only life-threatening infections for which other antimicrobials cannot be used are possible indications for quinolones in children, for example the use of ciprofloxacin in cystic fibrosis patients with a bronchopulmonary exacerbation, chronic suppurative otitis media caused by Pseudomonas sp., complicated urinary tract infections and enteritis caused by invasive multidrug-resistant pathogens (e.g. Salmonella, Shigella).