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Two methods are presented for the determination of cefuroxime and cefadroxil in human urine using first (1D) derivative spectrophotometry and high-performance liquid chromatography. Cefuroxime and cefadroxil were determined by measurement of their first-derivative amplitude in 0.1 N sodium hydroxide at 292.5 and 267.3 nm, respectively in the concentration range of 2-10 microg ml(-1) for each drug. The HPLC method depends upon using a LiChrospher 100 RP-18 (5 microm) column at ambient temperature for cefuroxime and 35 degrees C for cefadroxil with mobile phases consisting of water-acetonitrile-acetic acid (85:15:0.1 v/v) at a flow rate of 1.5 ml min(-1) for cefuroxime; and 0.02 M potassium dihydrogen phosphate-acetonitrile (95:5 v/v) containing 0.003% (w/v) hexanesulphonic acid sodium salt and adjusted to apparent pH 3 with phosphoric acid at a flow rate of 2 ml min(-1) for cefadroxil. Quantitation was achieved with UV detection at 275 and 260 nm for cefuroxime and cefadroxil, respectively, based on peak area with linear calibration curves at the concentration ranges of 2-10 microg ml(-1) for cefuroxime and 5-20 microg ml(-1) for cefadroxil. The proposed methods were applied to the determination of dissolution rate for tablets and capsules containing each drug. The urinary excretion patterns as the cumulative amounts excreted have been calculated for each drug using the proposed methods.
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An isocratic reversed-phase HPLC method was developed to determine cefepime levels in plasma and vitreous fluid. Cefepime and the internal standard cefadroxil were separated on a Shandon Hypersil BDS C18 column by using a mobile phase of 25 mM sodium dihydrogen phosphate monohydrate (pH 3) and methanol (87:13, v/v). Ultraviolet detection was carried out at 270 nm. The retention times were 4.80 min for cefepime and 7.70 min for cefadroxil. This fast procedure which involves an efficient protein precipitation step (addition of HClO4), allows a quantification limit of 2.52 microg ml(-1) and a detection limit of 0.83 microg ml(-1). Recoveries and absolute recoveries of cefepime from plasma were 96.13-99.44% and 94-102.5% respectively. The intra-day and inter-day reproducibilities were less than 2% for cefepime at 10, 30, 50 microg ml(-1) (n=10). The method was proved to be suitable for determining cefepime levels in human plasma and was modified to measure vitreous fluid samples.
The present study monitored medication prescribing patterns to patients treated for upper respiratory tract infections (URTIs) in the pediatric outpatient department (OPD) at Central Referral Hospital (CRH), Gangtok, Sikkim. A total of 562 URTI prescriptions of children, aged 0-12 years attending pediatric OPD at CRH, Sikkim were collected by a random once-weekly survey between May 2002 and April 2003. Males numbered 284 (50.5%), and females 278 (49.5%). Most of the patients in our study were aged 2-5 years (preschool children) (44.8%). The average number of medications prescribed per encounter was 2.37; 59.2% (789) of medicines were fixed-dose combination (FDC) products and two-thirds of FDCs were respiratory medicines (521). The most commonly prescribed medicines were respiratory medicines (47% of the total medicines prescribed). Others were antimicrobials (30.7%) and analgesic-antipyretics (18.8%). Among respiratory medicines, cough and cold preparations (prescribed in 13 different FDC products in 25 brand names) were prescribed most frequently (62%) followed by nasal preparations (21%) and beta(2) adrenergic agonist inhalers (9.2%). Ninety-eight percent of nasal preparations were isotonic saline drops (129). Antihistaminics (41.8%), non-opioid antitussives (13.5%), alpha agonist oral decongestants (42.3%), expectorants (32.2%), mucolytics (18.7%), paracetamol (14.7%), and beta(2) agonists (17.2%) were common ingredients of respiratory medicine combinations. Antihistamines (2.5%) and beta(2) agonists (9.2%) were used alone. The most commonly prescribed antimicrobial was amoxicillin with clavulanate (28.4%) followed by cefadroxil (20%), cotrimoxazole (9.5%) and amoxicillin alone (9.3%). Average number of antimicrobials prescribed was 0.7 (409/562). The most commonly prescribed analgesic-antipyretic was paracetamol (81.3%) followed by combination of ibuprofen and paracetamol (12.4%) and nimesulide (5.6%). Medication selection was rational in few cases. Various anomalies were observed in various aspects of drug use in children for URTI's. The main aim of the initiative is the need for more rational medicine use in URTIs in children for improvement of clinical effectiveness, cost effectiveness and reduction of potential useless risk of side effects.
The results of previous work performed in our laboratory using an in situ perfusion technique in rats and rabbit apical brush border membrane vesicles have suggested that the intestinal uptake of valacyclovir (VACV) appears to be mediated by multiple membrane transporters. Using these techniques, it is difficult to characterize the transport kinetics of VACV with each individual transporter in the presence of multiple known or unknown transporters. The purpose of this study was to characterize the interaction of VACV and the human intestinal peptide transporter using Chinese hamster ovary (CHO) cells that overexpress the human intestinal peptide transporter (hPEPT1) gene. VACV uptake was significantly greater in CHO cells transfected with hPEPT1 than in cells transfected with only the vector, pcDNA3. The optimum pH for VACV uptake was determined to occur at pH 7.5. Proton cotransport was not observed in hPEPT1/CHO cells, consistent with previously observed results in tissues and Caco-2 cells. VACV uptake was concentration dependent and saturable with a Michaelis-Menten constant and maximum velocity of 1.64 +/- 0.06 mM and 23.34 +/- 0.36 nmol/mg protein/5 min, respectively. A very similar Km value was obtained in hPEPT1/CHO cells and in rat and rabbit tissues and Caco-2 cells, suggesting that hPEPT1 dominates the intestinal transport properties of VACV in vitro. VACV uptake was markedly inhibited by various dipeptides and beta-lactam antibiotics, and Ki values of 12.8 +/- 2.7 and 9.1 +/- 1.2 mM were obtained for Gly-Sar and cefadroxil at pH 7.5, respectively. The present results demonstrate that VACV is a substrate for the human intestinal peptide transporter in hPEPT1/CHO cells and that although transport is pH dependent, proton cotransport is not apparent. Also, the results demonstrate that the hPEPT1/CHO cell system has use in investigating the transport kinetics of drugs with the human intestinal peptide transporter hPEPT1; however, the extrapolation of these transport properties to the in vivo situation requires further investigation.
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All antibiotics showed a significant urinary bactericidal activity against non-extended spectrum beta-lactamase Escherichia coli and Proteus mirabilis. Fluoroquinolones displayed high and persisting levels of urinary bactericidal activity against all gram-negative bacteria and Staphylococcus saprophyticus.
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Structural information on drug degradants and impurities can serve to accelerate the drug discovery and development cycle. Traditional structure elucidation methodologies for obtaining this information are often slow and resource-consuming; therefore, LC/MS profiling and LC/MS/MS substructural analysis methodologies have been developed to rapidly and accurately elucidate structures of impurities and degradants. This work is a further development of methodologies used for the elucidation of degradation products of paclitaxel [K.J. Volk et al., Proc. 9th AAPS Ann. Meeting, 1994, p.29]. In this study cefadroxil was used as a model compound for the evaluation of a predictive strategy for the production and elucidation of impurities and degradants induced by acid, base, and heat, using LC/MS and LC/MS/MS profiling methodology, resulting in an LC/MS degradant database which includes information on molecular structures, chromatographic behavior, molecular weight, UV data, and MS/MS substructural information. Furthermore, libraries such as this can provide a predictive foundation for pre-clinical development work involving drug stability, synthesis, and monitoring.
A pathogenetic bacterial strain X-1-06909 was isolated from naturally infected Siberian sturgeon in Beijing. The strain was identified according to its physiological and biochemical properties, and the sequence analysis of 16S rRNA gene. The drugs sensitivity was detected with Kirby-Bauer's agar diffusion method.
Patients with CARTI were prospectively recruited from 30 primary hospitals from December 2007 to July 2010. Those who had used antimicrobials within previous 2 weeks were excluded from the study. The clinical information such as temperature, white blood cell (WBC) count and percentage of neutrophils was recorded, and throat swab or deep cough sputum was collected to isolate pathogens. The specimens were collected and couriered to the Zhongshan Hospital microbiology laboratory within 2 h for bacterial culture. The minimal inhibition concentrations (MIC) of penicillin G, amoxicillin, cephradine, cephalexin, cefadroxil, sulfamethoxazole/trimethoprim and azithromycin were determined using the agar dilution test.
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1. Human serum protein binding of cefadroxil and some other cephalosporins were determined by centrifugal ultrafiltration (U.F.) method and equilibrium dialysis (E.D.) method. The binding rates of cefadroxil were 28.1% by U.F. method and 3.8% (beta 1*), 11.6% (beta 2*) by E.D. method. 2. Protein binding of cefadroxil with sera of various animal species were also determined by E.D. method. The binding rates were low as well as that with human serum. 3. With two popular calculation formula for E.D. method, binding rate was considered on the alteration of the ratio of V2/V1.