cefuroxime-axetil and cefetamet-pivoxyl

The serum bactericidal activity of three oral cephalosporins was studied in 12 volunteers, after administration of single doses of cefuroxime axetil 250 mg, cefixime 200 mg, cefixime 400 mg and cefetamet pivoxil 500 mg. Serum bactericidal activity against clinical isolates of Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae and Klebsiella pneumoniae was measured by a standardized microdilution method. Cefuroxime axetil demonstrated the best bactericidal activity against Gram-positive organisms and cefixime was the most bactericidal against Gram-negative bacteria.

Topics: Administration, Oral; Adolescent; Adult; Cefixime; Cefotaxime; Ceftizoxime; Cefuroxime; Cephalosporins; Cross-Over Studies; Female; Haemophilus influenzae; Humans; Klebsiella pneumoniae; Male; Serum Bactericidal Test; Streptococcus

The penetration of cefetamet and cefuroxime into the maxillary sinus mucosa after the administration of cefetamet pivoxil and cefuroxime axetil was investigated in patients undergoing elective surgery of the maxillary sinus. A total of 27 patients, 13 for cefetamet pivoxil and 14 for cefuroxime axetil, ranging from 15 to 70 years of age participated in this study. Each patient received three oral doses of either one tablet of cefetamet pivoxil (500 mg of GLOBOCEF) or two film tablets of cefuroxime axetil (125 and 250 mg of ZINAT) every 12 h. Sinus mucosa tissue samples were removed during surgery at times ranging from 2 to 4.5 h after the last oral administration. Blood samples were collected before drug administration, 2 h after the first and third doses, and concomitantly with tissue sample collection during surgery. All samples were analyzed by high-performance liquid chromatography. The concentrations of cefetamet and cefuroxime in plasma samples measured concomitantly with those in tissue samples ranged between 0.83 and 4.5 micrograms/ml for cefetamet and 0.59 and 3 micrograms/ml for cefuroxime. The mean tissue-to-plasma ratios calculated with reference to total (bound plus unbound) plasma drug concentrations were 0.60 (range, 0.52 to 0.77) for cefetamet (n = 4) and 0.38 (range, 0.28 to 0.44) for cefuroxime (n = 6). Both drugs seem to penetrate freely and easily into the sinus mucosa. The antibacterial activities of cefetamet pivoxil and cefuroxime axetil in cases of sinusitis therefore depend mainly on their achieved active plasma drug concentrations and their intrinsic activities in inhibiting the causative organism(s).

Topics: Adolescent; Adult; Aged; Ceftizoxime; Cefuroxime; Cephalosporins; Female; Humans; Male; Maxillary Sinus; Middle Aged; Mucous Membrane; Quality Control

Betalactams, mainly when orally administered, may lead to intestinal flora modifications related to their spectrum of activity, rate of absorption and degradation. therefore it is important to investigate the possible influence of recently developed oral cephem derivatives on normal human microflora. We have investigated the impact on normal human intestinal flora in a 10-day course with cefetamet-pivoxil (CET, 500 mg BID) in comparison to cefixime (CFX, 400 mg qD) or cefuroxime axetil (CA, 250 mg BID) in 24 patients suffering from acute exacerbation of chronic bronchitis. Stool specimens were taken before (day 0), at the end (day 10) and 14 days after treatment (day 24) and quali-quantitative microflora composition was determined with a detection limit of 10 CFU/g dry weight. Treatment with CET caused slight and non-significant modifications of normal intestinal flora. On the contrary CFX and CA significantly affect Enterobacteriaceae and clostridia with a concomitant increase in enterococci for CFX. With both CFX and CA there was a new appearance of Salmonella spp. as well as Clostridium difficile in 4 and 2 cases, respectively. Therefore CET seems to affect normal bowel flora minimally in comparison to other oral cephalosporins. This aspect might contribute to the low incidence of GI related side effects in patients treated with CEt for longer than 1 week.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacteria, Anaerobic; Bronchitis; Cefixime; Cefotaxime; Ceftizoxime; Cefuroxime; Cephalosporins; Chronic Disease; Clostridium; Enterobacteriaceae; Enterococcus; Feces; HeLa Cells; Humans; Intestines; Microbial Sensitivity Tests; Middle Aged

The levels of degradation of cefetamet pivoxil (CAT), cefuroxime axetil (CAE), and cefpodoxime proxetil (CPD) in 0.6 M phosphate buffer (pH 7.4) and human intestinal juice (pH 7.4) at 37 degreesC over 24 h were compared. Significant differences in the time courses of degradation and in the patterns of degradation products were observed. (i) The relative proportions of the Delta2- and Delta3-cephalosporins were roughly reversed in the two incubation media. In phosphate buffer, the major degradation product was the Delta2-cephalosporin (CAT = 61%; CAE = 74%; CPD = 85%), while in intestinal juice it was the Delta3-cephalosporin (CAT = 86%; CAE = 75%; CPD = 87%). (ii) Generally, the degradation of the prodrug esters progressed faster in intestinal juice than in phosphate buffer (e.g., for CAT the half-lives [t1/2s] were 0.78 and 4.3 h, respectively). (iii) The two diastereoisomers of CAE and CPD were degraded at different rates in intestinal juice (for the CAE diasteroisomers, t1/2s = 0.37 and 0.93 h; for the CPD diastereoisomers, t1/2s = 0.18 and 0.98 h) but were degraded at similar rates in phosphate buffer (for the CAE diastereoisomers, t1/2 = 1.6 h; for the CPD t1/2 diastereoisomers, = 2.2 h). It is concluded that (i) the Delta2 isomerization does not significantly affect the bioavailability of prodrug esters since enzymatic hydrolysis in the intestinal fluid proceeds mainly to the active Delta3-cephalosporin and (ii) the high degree of stereoselectivity of the enzymatic ester hydrolysis should make it possible to increase the bioavailabilities of certain prodrug esters (CAE, CPD) by using the more stable diasterioisomer.

Topics: Administration, Oral; Adult; Biological Availability; Cefpodoxime Proxetil; Ceftizoxime; Cefuroxime; Cephalosporins; Drug Stability; Humans; Intestinal Mucosa; Male; Prodrugs