Comparison of cefadroxil and cephalexin in the treatment of community-acquired pneumonia. (25/31)

Thirty-four patients with community-acquired acute pneumonias were treated in a prospective, randomized trial with either cefadroxil, 500 mg twice daily, or cephalexin, 250 mg four times daily. In both groups of patients, the presence of chronic illnesses predisposing to pneumonia was common. Streptococcus pneumoniae was isolated from 65% of the initial sputum specimens, and most illnesses were of mild to moderate severity. All 19 cases treated with cefadroxil and all 15 cases treated with cephalexin were clinically cured, and adverse reactions to the medications were minimal. The success of these regimens suggests that outpatient use of oral cephalosporin therapy may be an appropriate treatment of patients with mild or moderate community-acquired pneumonia.  (+info)

Pharmacokinetics of cefadroxil after oral administration in humans. (26/31)

The human oral pharmacokinetics of cefadroxil were studied in parallel at doses of 250, 500, and 1,000 mg in three groups of 10 healthy young male volunteers. Renal excretion of intact cefadroxil, accounted for 82, 79, and 77% of the above doses. Mean peak serum levels were dose linear: 9, 18, and 35 microgram/ml at 250, 500, and 1,000 mg, respectively. However, overall pharmacokinetics were linear only in the 250- to 500-mg dose range; apparent serum clearances were 10 liters/h, and true renal clearances were 9 and 8 liters/h at 250 and 500 mg. At 1,000 mg, apparent serum clearance dropped to about 7 liters/h, true renal clearance, dropped to 6 liters/h, and the area under the curve increased disproportionately. At 250 and 500 mg, mean half-life was about 1.2 h; at 1,000 mg, however, it was 1.6h. The nonlinear decrease in clearance could be related to saturation of active renal tubular secretion of cefadroxil between the 500- and 1,000-mg doses. Previous results indicating that cefadroxil has greater persistence than other oral cephalosporins such as cephalexin, cephradine, cefaclor were confirmed.  (+info)

Pharmacokinetics of cefadroxil and cefaclor during an eight-day dosage period. (27/31)

The concentrations of cefadroxil and cefaclor in serum were studied in eight healthy volunteers receiving 1,000 mg of both substances three times per day for 8 days. Intraindividual comparisons showed an increase in peak serum levels of cefadroxil from days 1 to 8 in seven of eight volunteers. Cefaclor peak concentrations did not rise during the 8 days.  (+info)

Differential recognition of beta -lactam antibiotics by intestinal and renal peptide transporters, PEPT 1 and PEPT 2. (28/31)

This study was initiated to determine if there are differences in the recognition of beta -lactam antibiotics as substrates between intestinal and renal peptide transporters, PEPT 1 and PEPT 2. Reverse transcription-coupled polymerase chain reaction and/or Northern blot analysis have established that the human intestinal cell line Caco-2 expresses PEPT 1 but not PEPT 2, whereas the rat proximal tubule cell line SKPT expresses PEPT 2 but not PEPT 1. Detailed kinetic analysis has provided unequivocal evidence for participation of PEPT 2 in SKPT cells in the transport of the dipeptide glycylsarcosine and the aminocephalosporin cephalexin. The substrate recognition pattern of PEPT 1 and PEPT 2 was studied with cefadroxil (a cephalosporin) and cyclacillin (a penicillin) as model substrates for the peptide transporters constitutively expressed in Caco-2 cells (PEPT 1) and SKPT cells (PEPT 2). Cyclacillin was 9-fold more potent than cefadroxil in competing with glycylsacosine for uptake via PEPT 1. In contrast, cefadroxil was 13-fold more potent than cyclacillin in competing with the dipeptide for uptake via PEPT 2. The substrate recognition pattern of PEPT 1 and PEPT 2 was also investigated using cloned human peptide transporters functionally expressed in HeLa cells. Expression of PEPT 1 or PEPT 2 in HeLa cells was found to induce H(+)-coupled cephalexin uptake in these cells. As was the case with Caco-2 cells and SKPT cells, the uptake of glycylsarcosine induced in HeLa cells by PEPT 1 cDNA and PEPT 2 cDNA was inhibitable by cyclacillin and cefadroxil. Again, the PEPT 1 cDNA-induced dipeptide uptake was inhibited more potently by cyclacillin than by cefadroxil, and the PEPT 2 cDNA-induced dipeptide uptake was inhibited more potently by cefadroxil than by cyclacillin. It is concluded that there are marked differences between the intestinal and renal peptide transporters in the recognition of beta -lactam antibiotics as substrates.  (+info)

Expression cloning and functional characterization of the kidney cortex high-affinity proton-coupled peptide transporter. (29/31)

The presence of a proton-coupled electrogenic high-affinity peptide transporter in the apical membrane of tubular cells has been demonstrated by microperfusion studies and by use of brush border membrane vesicles. The transporter mediates tubular uptake of filtered di- and tripeptides and aminocephalosporin antibiotics. We have used expression cloning in Xenopus laevis oocytes for identification and characterization of the renal high-affinity peptide transporter. Injection of poly(A)+ RNA isolated from rabbit kidney cortex into oocytes resulted in expression of a pH-dependent transport activity for the aminocephalosporin antibiotic cefadroxil. After size fractionation of poly(A)+ RNA the transport activity was identified in the 3.0- to 5.0-kb fractions, which were used for construction of a cDNA library. The library was screened for expression of cefadroxil transport after injection of complementary RNA synthesized in vitro from different pools of clones. A single clone (rPepT2) was isolated that stimulated cefadroxil uptake into oocytes approximately 70-fold at a pH of 6.0. Kinetic analysis of cefadroxil uptake expressed by the transporter's complementary RNA showed a single saturable high-affinity transport system shared by dipeptides, tripeptides, and selected amino-beta-lactam antibiotics. Electrophysiological studies established that the transport activity is electrogenic and affected by membrane potential. Sequencing of the cDNA predicts a protein of 729 amino acids with 12 membrane-spanning domains. Although there is a significant amino acid sequence identity (47%) to the recently cloned peptide transporters from rabbit and human small intestine, the renal transporter shows distinct structural and functional differences.  (+info)

Functional analysis of a chimeric mammalian peptide transporter derived from the intestinal and renal isoforms. (30/31)

l. Recently two genes have been identified by expression cloning that encode mammalian epithelial peptide transporters capable of translocating di- and tripeptides and selected peptidomimetics by stereoselective and rheogenic substrate-H+ cotransport. PepT1 from rabbit or human small intestine induces a transport activity with high transport capacity but rather low substrate affinity when expressed in Xenopus oocytes. In contrast, the renal carrier PepT2 is a high affinity-type transporter with a lower maximal transport capacity. In addition, both transporters show differences in pH dependence and substrate specificity. 2. As a first approach to identify structural components of the transport proteins that determine their phenotypical characteristics, we constructed a recombinant chimeric peptide transporter (CH1Pep) in which the aminoterminal region (residues 1-401) is derived from PepT2 whereas the carboxyterminal region (residues 402-707) starting at the end of transmembrane domain 9 is derived from PepT1. Expression of PepT1, PepT2 and CH1Pep in Xenopus oocytes allowed the characteristics of the transporters to be determined by flux studies employing a radiolabelled dipeptide and by the two-electrode voltage clamp technique. 3. Our studies indicate that CH1Pep conserves the characteristics of PepT2 including the high affinity for dipeptides and peptidomimetics, the substrate specificity, the pH dependence of transport activation and the electrophysiological parameters. We conclude that the phenotypical characteristics of the renal peptide transporter are determined by its amino-terminal region.  (+info)

In-vitro activity of 21 beta-lactam antibiotics against penicillin-susceptible and penicillin-resistant Streptococcus pneumoniae. (31/31)

MICs of 21 beta-lactams were determined by agar dilution against 283 penicillin-susceptible (pen-S), 122 intermediate (pen-I) and 23 fully penicillin-resistant (pen-R) pneumococci. MICs of all beta-lactams increased with increasing MICs of penicillin. Clometocillin was the most active penicillin against pen-I or pen-R pneumococci. All oral cephalosporins except cefuroxime and cefpodoxime were less active than penicillin and none was satisfactory against pen-I or pen-R pneumococci. The parenteral third- and fourth-generation cephalosporins (except ceftazidime) were similar in activity to penicillin against pen-S isolates. Cefpirome showed the lowest mean MICs against pen-I and pen-R strains.  (+info)