A new chemiluminescence reaction, the luminol-Cu(2+) reaction, was investigated for the determination of thirteen (13) cephalosporin antibiotics, namely cefalexin, cefadroxil, cefradine, cefazolin sodium, cefaclor, cefuroxime axetil, cefotaxime sodium, cefoperazone sodium, ceftriaxone sodium, ceftazidime, cefetamet pivoxil hydrochloride, cefixime, and cefpodoxime. It was found that, without adding any special oxidant, strong chemiluminescent (CL) signal could be produced from the reaction of the alkaline luminol with the above-mentioned antibiotics in the presence of Cu(2+). The experimental conditions for the reaction were carefully optimized with flow-injection mode. The detection limits are 0.3 ng/mL cefalexin, 3 ng/mL cefadroxil, 0.3 ng/mL cefradine, 0.02 μg/mL cefazolin sodium, 0.8 ng/mL cefaclor, 0.02 μg/mL cefuroxime axetil, 5 ng/mL cefotaxime sodium, 0.02 μg/mL cefoperazone sodium, 0.8 ng/mL ceftriaxone sodium, 1 ng/mL ceftazidime, 0.08 ng/mL cefetamet pivoxil hydrochloride, 0.8 ng/mL cefixime, and 2 ng/mL cefpodoxime. The proposed method was validated by direct application to commercial formulations and spiked milk samples containing cefradine. A possible reaction mechanism is also discussed.
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The therapeutic efficacy of 25 mg/kg of cefadroxil administered once daily was compared with that of 50 mg/kg/day of ampicillin administered in four equal doses in the treatment of acute uncomplicated urinary tract infections (UTIs) in children. Nineteen girls and seven boys (mean age, 5.5 years) received cefadroxil, and 18 girls and eight boys (mean age, 5.9 years) received ampicillin. The clinical and bacteriological characteristics, as well as the demographic characteristics, of both populations were well matched. Patients with structural anomalies or with a history of hypersensitivity to cephalosporins or penicillins or abnormal hepatorenal function were excluded from the trial. Only patients with at least two consecutive positive cultures of a single pathogen, obtained in clean-catch midstream urine samples (greater than or equal to 10(5) colony-forming units per ml urine) and susceptible to the respective antibiotic, were admitted to the study. Urine cultures were repeated during the ten days of treatment and ten days after the completion of treatment. All patients in the cefadroxil group were evaluated as clinically and bacteriologically cured. Three (12%) of the patients in the ampicillin group had positive cultures in the immediate post-treatment period. The differences in the cure rates of the two groups were not statistically significant. No adverse effects of either antibiotic were observed.
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A selective and sensitive liquid chromatography tandem mass spectrometry method (LC-MS/MS) was developed and validated for the determination of cefdinir in rat plasma and urine. Following a simple protein precipitation using methanol, chromatographic separation was achieved with a run time of 10 min using a Synergi 4 µ polar-RP 80A column (150 × 2.0 mm, 4 µm) with a mobile phase consisting of 0.1% formic acid in water and methanol (65:35, v/v) at a flow rate of 0.2 mL/min. The protonated precursor and product ion transitions for cefdinir (m/z 396.1 → 227.2) and cefadroxil, an internal standard (m/z 364.2 → 208.0) were monitored in the multiple reaction monitoring in positive ion mode. The calibration curves for plasma and urine were linear over the concentration range 10-10,000 ng/mL. The lower limit of quantification was 10 ng/mL. All accuracy values were between 95.1 and 113.0% and the intra- and inter-day precisions were <13.0% relative standard deviation. The stability under various conditions in rat plasma and urine was also found to be acceptable at three concentrations. The developed method was applied successfully to the pharmacokinetic study of cefdinir after oral and intravenous administration.
The cure rate of acute uncomplicated urinary tract infection in general practice using 3 different treatment regimens, was studied in a randomized, multicenter trial. Patients were assigned to receive either cefadroxil 1 g once daily for 3 or 7 days or amoxycillin 375 mg t.i.d. for 7 days. 310 patients entered the study, of whom 230 could be evaluated according to the protocol. Two thirds of the cases were due to infections with Escherichia coli and about one fourth to Staphylococcus saprophyticus. No statistically significant differences in cure rates between the 3 regimens could be demonstrated neither at 1 week nor at 5 weeks of follow-up. The frequency of adverse reactions was low and similar in each treatment group.
The transport characteristics of the aminocephalosporin [3H]cefadroxil have been studied in brush-border membrane vesicles (BBMV) of rat kidney cortex by a rapid filtration technique and by use of a potential sensitive fluorescent dye. Influx of [3H]cefadroxil (0.25 microM) into BBMV as a function of time displayed a pronounced overshoot phenomenon in the presence of a transmembrane pH gradient (pHin > pHout). Evidence for an electrogenic cefadroxil/H+-symport in the presence of an inwardly directed proton gradient is provided by the demonstration of: 1) reduced uptake in the presence of a protonophore; 2) reduced uptake under voltage clamp conditions; and 3) increased uptake in the presence of a valinomycin-induced inside negative K+-diffusion potential. pH-gradient dependent uptake of [3H]cefadroxil as a function of substrate concentration revealed the presence of multiple carrier systems. By kinetic analysis, a high-affinity carrier system (Km, 8.8 +/- 1.3 microM) and a low-affinity system (Km, 2.62 +/- 0.80 mM) could be resolved. The high-affinity transport system was found to be very specific for substrates (cephalosporins and di- and tripeptides) carrying an alpha-amino group. By use of a potential sensitive fluorescent dye 3,3'-dipropylthiadicarbocyanine iodide, the low-affinity transport system was characterized with respect to its driving force and its kinetic features. This transporter was found also to be electrogenic in nature, representing a second cefadroxil/H+-symport system. In summary, our studies demonstrate for the first time uphill transport of cefadroxil in kidney BBMV mediated by multiple carrier systems. Transport is rheogenic, energized by the proton motive force and shared by other aminocephalosporins as well as di- and tripeptides.(ABSTRACT TRUNCATED AT 250 WORDS)
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A beta-lactam antibiotic, amoxicillin, was microencapsulated with ethylcellulose using a solvent evaporation process in liquid paraffin containing sorbitan tristearate as a dispersing agent, and the microcapsules obtained showed first-order drug release. Usage of the previous log-log relationship of cefadroxil between in vitro dissolution half-lives (T50) and the experimental release rate constants (k'r) of the drug in vivo, and the nomogram for the design of satisfactory sustained-release preparations resulted in the prediction that ethylcellulose microcapsules containing 60% amoxicillin would show the most effective sustained-release pattern. Prepared microcapsules containing various amounts of amoxicillin were administered to beagle dogs and it was found that above prediction was correct. In addition, a more precise log-log correlation concerning amoxicillin was also undertaken, good linearity was observed and the decline was very similar to that of cefadroxil.
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Investigation was made on the therapeutic effect of a new antibiotic, cefatrizine(CFT), in oral infections according to the following procedure. Results are summarized as follows. Determination was made on the MIC of CFT against 8 clinical isolates of S. epidermidis, 5 of S. aureus and 7 of E. coli in comparison with those of CEX and PBPC. MICs of CFT against S aures were demonstrated 3.13 to 6.25 mcg/ml which were superior to those of CEX and ABPC. CFT was administered orally in a dose of 500 mg at an hour and a half before the extraction of the impacted wisdom tooth in the mandibula. During the operation, gingival and blood specimens were collected and each CFT level was determined. The mean CFT level in the gingiva reached to 0.95 mcg/ml and that in the blood to 5.77 mcg/ml. According to these experimental results, CFT was administered to patients with moderate oral infection at a dose of 500 mg and clinical assessment was made according to the criteria established by Japanese Society of Oral Surgeons. As the results, the effectiveness rate of CFT was 85%. No serious side effect was observed. From the results of the present study, CFT may be effective for moderate oral surgery infections.
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In vitro susceptibility testing of 28 strains of Eikenella corrodens by the agar dilution technique showed that all strains were uniformly susceptible to penicillin, ticarcillin, cefoxitin, cefotaxime, N-formimidoyl thienamycin, and moxalactam and resistant to clindamycin and cefadroxil. Cefoperazone, piperacillin, and mezlocillin showed good activity, with some strains relatively resistant. Bacampicillin and cefamandole showed relatively poor activity.
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A meta-analysis was conducted to compare the efficacy and safety of oral cefadroxil monohydrate (30 mg/kg QD or 15 mg/kg BID) with that of oral penicillin V (8, 10, or 15 mg/kg BID, TID, or QID) in the treatment of group A beta-hemolytic streptococcal (GABHS) pharyngitis and tonsillitis treated for 10 days. A simple random effects model was used for combining the efficacy and safety results of nine comparative trials performed in the United States. A total of 1646 patients aged < or = 19 years were considered evaluable; 1406 patients were evaluable using revised bacteriologic criteria, and 1499 patients were considered fully evaluable for safety. The results demonstrate significantly better response rates (P < 0.05) with cefadroxil monohydrate than with penicillin V for overall cure (91.8% versus 81.3%), bacteriologic cure (92.6% versus 81.4%), and bacteriologic recurrence (4.2% versus 10.5%); clinical cure rates were statistically similar (90.5% versus 90.2%). Revised bacteriologic criteria analysis revealed bacteriologic cure rates of 95.8% versus 88.7% (P < 0.05) and bacteriologic recurrence rates of 4.9% versus 7.1% (P = NS) for cefadroxil monohydrate and penicillin V, respectively. Adverse events related to drug administration occurred infrequently and did not differ significantly between treatment groups (P > 0.05). Compliance with cefadroxil monohydrate was at least as good as with penicillin V. Penicillin is currently the drug of choice in the treatment of GABHS pharyngitis and tonsillitis. Based on the information described in this large meta-analysis, cefadroxil monohydrate is an excellent alternative to oral penicillin V in the treatment of GABHS pharyngitis and tonsillitis.
This study was designed to compare the in vitro activities of recent cephalosporins and other beta-lactams. One of our objectives was to determine whether the microbiologist could use a single cephalosporin for routine antibiotic sensitivity testing. All the strains studied were recovered from outpatients. Sensitivity and/or resistance were evaluated by MIC determination, according to a program developed in our laboratory, using a personal computer. Using special programs, patterns of activities of beta-lactams were determined quantitatively and graphically for each bacterial strain tested. For most strains ceftriaxone, and to a lesser extent moxalactam and cefoperazone, exhibited greater antibacterial activity than the other beta-lactams, except against group D streptococci. For Enterobacteriaceae, cefadroxil is satisfactory in screening for in vitro activity of cephalosporins.
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The reabsorption of filtered di- and tripeptides as well as certain peptide mimetics from the tubular lumen into renal epithelial cells is mediated by an H+-coupled high-affinity transport process. Here we demonstrate for the first time H+-coupled uptake of dipeptides into the renal proximal tubule cell line LLC-PK1. Transport was assessed 1) by uptake studies using the radiolabeled dipeptide D-[3H]Phe-L-Ala, 2) by cellular accumulation of the fluorescent dipeptide D-Ala-Lys-AMCA, and 3) by measurement of intracellular pH (pHi) changes as a consequence of H+-coupled dipeptide transport. Uptake of D-Phe-L-Ala increased linearly over 11 days postconfluency and showed all the characteristics of the kidney cortex high-affinity peptide transporter, e.g., a pH optimum for transport of D-Phe-L-Ala of 6.0, an apparent Km value for influx of 25.8 +/- 3. 6 microM, and affinities of differently charged dipeptides or the beta-lactam antibiotic cefadroxil to the binding site in the range of 20-80 microM. pHi measurements established the peptide transporter to induce pronounced intracellular acidification in LLC-PK1 cells and confirm its postulated role as a cellular acid loader.
The susceptibility of 24 strains of Eikenella corrodens was determined, by the agar dilution technique, to 10 cephalosporins, as well as to clindamycin, penicillin and dicloxacillin. All strains were uniformly very susceptible to penicillin G and cefoxitin and resistant to clindamycin and dicloxacillin. Cefazolin showed good activity. Cephalexin, cephradine, and cefadroxil showed poor activity, and cefamandole's activity was relatively poor. Cephalothin, cephapirin, cefaclor, and cephaloridine showed moderate activity, with some strains relatively resistant.
The transport characteristics of cefadroxil, an aminocephalosporin antibiotic, across the brush border membrane of rat small intestine were investigated by a rapid filtration technique. The uptake of cefadroxil was not affected by Na+ gradient, suggesting the absence of a cotransport system between cefadroxil and Na+ in the brush border membrane. The uptake was slightly inhibited by HgCl2 pretreatment and stimulated by the countertransport effect, where cyclacillin played a role as an elicitor. These results suggest the existence of a carrier-mediated transport system for cefadroxil in the brush border membrane, which is shared with cyclacillin. Papain treatment increased the specific transport activities for the antibiotic. This may be the first step of purification of the cefadroxil transport carrier.
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The study was conducted in 3 retail pharmacies in Sarjapur area, Bangalore East. The duration of the study was for a period of 10 days from August 1st to August 10th 2014. The common complaints for which the patients frequented the pharmacies were observed and recorded .The investigator personally interviewed the patients between 6pm to 9pm, near the respective pharmacies. During this study period around 216 patients visited pharmacies without prescription. The drugs supplied to 216 patients by private pharmacies without prescription was recorded. Data was analysed by descriptive statistics using Microsoft Excel.
We examined the peptide transport activity in renal basolateral membranes. [(14)C]glycylsarcosine (Gly-Sar) uptake in rat renal cortical slices was saturable and inhibited by excess dipeptide and aminocephalosporin cefadroxil. When several renal cell lines were screened for the basolateral peptide transport activity, Madin-Darby canine kidney (MDCK) cells were demonstrated to have the greatest transport activity. [(14)C]Gly-Sar uptake across the basolateral membranes of MDCK cells was inhibited by di- and tripeptide and decreased with decreases in extracellular pH from 7.4 to 5.0. The Michaelis-Menten constant value of [(14)C]Gly-Sar uptake across the basolateral membranes of MDCK cells was 71 microM. The basolateral peptide transporter in MDCK cells showed several different [(14)C]Gly-Sar transport characteristics in growth dependence, pH profile, substrate affinity, and sensitivities to chemical modifiers from those of the apical H(+)-peptide cotransporter of MDCK cells. The findings of the present investigation indicated that the peptide transporter was expressed in the renal basolateral membranes. In addition, from the functional characteristics, the renal basolateral peptide transporter was suggested to be distinguishable from known peptide transporters, i.e., H(+)-peptide cotransporters (PEPT1 and PEPT2) and the intestinal basolateral peptide transporter.
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The increasing resistance of E. coli to trimethoprim makes this drug less suitable for empiric treatment of UTI. Young children with UTI seem predisposed to early development of resistance. Therefore, surveillance of resistance to antimicrobials with special regard to age and gender is recommended.
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There are several risk factors for the colonisation, infection and spreading of antibiotic resistant bacteria among elderly residents of nursing homes. An updated estimate of the native prevalence of antimicrobial resistance in uropathogens among Swedish nursing home residents is needed.
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The aim of this study was to examine the role of PEPT2, a proton-coupled oligopeptide transporter of the SLC15 family, on the disposition of the antibiotic cefadroxil in the body, particularly the kidney and brain. Pharmacokinetic, tissue distribution, and renal clearance studies were performed in wild-type and PEPT2 null mice after intravenous bolus administration of [(3)H]cefadroxil at 1, 12.5, 50, and 100 nmol/g body weight. Studies were also performed in the absence and presence of probenecid and quinine. Cefadroxil disposition kinetics was clearly nonlinear over the dose range studied (1-100 nmol/g), which was attributed to both saturable renal tubular secretion and reabsorption of the antibiotic. After an intravenous bolus dose of 1 nmol/g cefadroxil, PEPT2 null mice exhibited a 3-fold greater total clearance and 3-fold lower systemic concentrations of drug compared with wild-type animals. Renal clearance studies further demonstrated that the renal reabsorption of cefadroxil was almost completely abolished in PEPT2 null versus wild-type mice (3% versus 70%, p < 0.001). Of the 70% of cefadroxil reabsorbed in wild-type mice, PEPT2 accounted for 95% and PEPT1 accounted for 5% of reabsorbed substrate. Tissue distribution studies indicated that PEPT2 had a dramatic effect on cefadroxil tissue exposure, especially in brain where the cerebrospinal fluid (CSF)-to-blood concentration ratio of cefadroxil was 6-fold greater in PEPT2 null mice compared with wild-type animals. These findings demonstrate that renal PEPT2 is almost entirely responsible for the reabsorption of cefadroxil in kidney and that choroid plexus PEPT2 limits the exposure of cefadroxil (and perhaps other aminocephalosporins) in CSF.
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Violacein works synergistically with most commercial antibiotics and could be used as drug in combination with other antimicrobial agents.
The aerobic and anaerobic flora from gingival pockets of 49 dogs with severe gingivitis and periodontitis were cultured. The susceptibility of each isolate to four antimicrobial agents currently approved for veterinary use in the USA (amoxicillin-clavulanic acid; clindamycin; cefadroxil; and enrofloxacin) was determined. Amoxicillin-clavulanic acid (Clavamox Pfizer Animal Health) had the highest in-vitro susceptibility against all isolates (96%), all aerobes (94%) and all anaerobes (100%) tested. For gram-negative aerobes, enrofloxacin (Baytril, Bayer Corp.) had the highest in-vitro susceptibility activity. For bacteria associated with treatment of gingivitis, which typically are mixed aerobic/anaerobic and gram-positive/gram-negative organisms, the antimicrobial of choice for clinical use based on these susceptibility tests is amoxicillin-clavulanic acid.
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Fast Disintegrating Tablets (FDTs) is a rapidly growing dosage form preferred for special population (pediatric, geriatric and psychotic patients). It is also developed with the aim of improving bioavailability and patient compliance. During the present study, cefadroxil fast disintegrating tablets formulations (n=9) were designed and optimized by central composite design with two independent variables (croscarmellose and crospovidone) using design expert® software. The effects of independent variables on formulation properties such as friability, hardness, in vitro dispersion and disintegration were assessed by drawing response surface graphs with design expert® software. Tablets were assessed for pharmacopeial and non-pharmacopeial parameters to ensure the quality of compressed tablets. Among all formulations, F3, F8 and F9 have shown better results. The formulation F9 containing 15mg croscarmellose and 33.075mg crospovidone showed good pharmacotechnical attributes as well as shelf life. F 9 showed improved dissolution with t90% of> 2 min and will lead to better bioavailability.
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The beta-lactam antibiotic oral absorption pathway is studied using a single-pass perfusion technique in the rat small intestine. Beta-lactam antibiotic absorption in the presence of amino acids, small peptides, and other beta-lactams is modeled using a simple competitive inhibition boundary condition at the intestinal wall, with a corrected value for the intestinal wall concentration, Cw, derived from the modified boundary layer analysis. The model-predicted permeability in the presence of an inhibitor is used to characterize the beta-lactam antibiotic intestinal carrier system. Several concentrations of cephalexin, coperfused with a constant concentration of cefadroxil (equal to its Km), showed that the Km of cephalexin approximately doubled from 7.2 (+/- 1.1) to 18.8 (+/- 4.1) mM; Jmax remained unchanged at 9.2 (+/- 1.2) and 11.1 (+/- 2.1) mM; and the carrier permeability, Pc, was reduced by approximately 50% from 1.11 (+/- 0.10) to 0.59 (+/- 0.04), consistent with competitive absorption kinetics. The predicted in situ wall permeability, the mean value of P*w, of beta-lactams perfused in the presence of other beta-lactams was calculated and then compared with experimentally determined values. For cefadroxil, P*w = 0.27 (+/- 0.04), the mean value of P*w = 0.29; for cefatrizine, P*w = 0.67 (+/- 0.09), the mean value of P*w (+/- 0.09), the mean value of P*w = 0.59; and for cephalexin, P*w = 0.56 (+/- 0.05), the mean value of P*w = 0.59.(ABSTRACT TRUNCATED AT 250 WORDS)
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Cefadroxil 1 g twice daily and amoxycillin 500 mg three times a day were compared in 111 patients suffering from acute exacerbations of chronic bronchitis. Treatment was for seven days. Excellent or good clinical responses were found in 85 per cent of cases receiving cefadroxil and 81 per cent of patients taking amoxycillin. However, residual symptoms of cough and rhonchi were present to a statistically significantly greater extent in the amoxycillin group. Tolerance of both drugs was good with mild to moderate side effects reported in seven of 54 patients in the cefadroxil group and six of 56 patients taking amoxycillin. Severe nausea and vomiting in two cases in the amoxycillin group resulted in discontinuation of therapy. Microbiological examination of sputum samples showed pathogenic bacteria in 16 per cent, principally Haemophilus influenzae. Amoxycillin 500 mg tds and cefadroxil 1 g bd were equally effective in the treatment of acute exacerbations of chronic bronchitis.
The ECO.SENS study investigated the prevalence and antimicrobial susceptibility of pathogens causing community-acquired acute uncomplicated urinary tract infections (UTIs) in 4734 women aged 18-65 years presenting with symptoms of acute UTI, at 252 community healthcare centres in 16 countries in Europe plus Canada. Resistance in Escherichia coli occurred most frequently to ampicillin (30%) and sulphonamides (29%), followed by trimethoprim (15%), trimethoprim/sulphamethoxazole (14%) and nalidixic acid (5%) but was low to co-amoxiclav, mecillinam, cefadroxil, nitrofurantoin, fosfomycin, gentamicin and ciprofloxacin, all at<3%. Consumption of antibiotics in 1997 varied more than 4-fold within Europe and from 9 to 37 DDD/1000 inhabitants/day, the consumption being highest in Southern Europe. The consumption of broad-spectrum penicillins correlated with resistance to ampicillin and there was a clear correlation between quinolone consumption and resistance to ciprofloxacin and nalidixic acid. The 4-fold difference in antibiotic consumption within Europe and the correlation to resistance emphasises the importance of controlling antibiotic usage.
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The agar dilution method was used to determine the inhibitory activity of 25 antimicrobial agents against 69 strains of Dichelobacter nodosus and 108 strains of the genus Fusobacterium, all of which were isolated from 90 clinical cases of ovine footrot between October 1998 and November 2000. In the case of the micro-organisms belonging to the genus Fusobacterium, the six beta-lactams studied (benzyl penicillin, ampicillin, cloxacillin, cefadroxil, cefuroxime and cephalexine) proved to be, in general, the most effective antimicrobial agents. Chloramphenicol, clindamycin and doxycycline were also quite active against Fusobacterium spp. With regard to the 69 strains of D. nodosus tested, the levels of resistance remain low.
The mechanisms of renal excretion of cefadroxil were investigated in conscious rats. The drug was intravenously infused at several infusion rates (0.27, 1.08, 5.40, 12.00, and 31.35 mg/hr), and the total and renal clearances were determined after the steady-state was reached. Renal clearance accounted for approximately 91% of total clearance. Renal clearance of cefadroxil increased from 2.51 +/- 0.39 to 3.57 +/- 0.43 ml/min as the steady-state cefadroxil plasma concentration increased from 1.7 +/- 0.3 to 24.4 +/- 3.8 micrograms/ml, and this has been attributed to a saturable renal tubular reabsorption of the antibiotic. The ratio of unbound cefadroxil renal clearance to glomerular filtration rate was larger than unity, which indicates that the antibiotic also undergoes active renal tubular secretion. When cefadroxil was administered together with cephalexin, an increase in the renal clearance of cefadroxil was observed, which has been attributed to a competitive inhibition of the tubular reabsorption of cefadroxil by cephalexin. A pharmacokinetic model for the renal excretion of cefadroxil was developed, and mathematical expressions showing the relationship between renal clearance and steady-state plasma concentration were deduced.
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Survey of 1000 US pediatricians in 1991, chosen randomly from the membership of the American Academy of Pediatrics. The survey included questions related to 2 clinical scenarios, respondent demographics, and knowledge of streptococcal pharyngitis.