OBJECTIVE: To establish a new high performance liquid chromatography (HPLC) method for determining the concentration of cefazolin, cefradine, cefoperazone and cefotaxime in blood and urine, as well as to investigate its applicability. METHODS: Protein in blood and urine was precipitated directly by acetonitrile with acetanilide was used as the internal standard using Agilent Zorbax SB-Aq column (250 mm x 4.6 mm, 5 microm). The mixed solvents of water (triethylamine 0.12%, acetic acid 0.12%) and acetonitrile were used as the mobile phase to separate cephalosporins using gradient elution method at 1 mL/min (flow rate) and 254 nm (detection wavelength). RESULTS: The working curve of four cephalosporins showed a good correlation (r = 0.9993), with the detection limit up to 0.01 microg/mL. The recovery rate was more than 81.2%. CONCLUSION This method is fast, easy and accurate. It is suitable for biological analysis of the 4 cephalosporins of the blood and urine in practical cases.
Adult ; Anti-Bacterial Agents/urine* ; Cefazolin/urine* ; Cefoperazone/urine* ; Cefotaxime/urine* ; Cephalosporins/urine* ; Cephradine/urine* ; Chromatography, High Pressure Liquid/methods* ; Forensic Toxicology ; Humans ; Male ; Sensitivity and Specificity ; Specimen Handling

The pharmacokinetics and dosage regimen of cefotaxime following its single subcutaneous administration (10 mg/ kg) were investigated in buffalo calves. Plasma and urine samples were collected over 10 and 24 h post administration, respectively. Cefotaxime in plasma and urine was estimated by microbiological assay technique using E. coli as test organism. The pharmacokinetic profiles fitted one-compartment open model. The peak plasma levels of cefotaxime were 6.48 +/- 0.52 microgram/ml at 30 min and the drug was detected upto 10 h. The absorption half-life and elimination halflife were 0.173 +/- 0.033 h and 1.77 +/- 0.02 h, respectively. The apparent volume of distribution and total body clearance were 1.17 +/- 0.10 l/kg and 0.45 +/- 0.03 l/kg/h, respectively. The urinary excretion of cefotaxime in 24 h, was 5.36 +/- 1.19 percent of total administrated dose. A satisfactory subcutaneous dosage regimen for cefotaxime in buffalo calves would be 13 mg/kg repeated at 12 h intervals.
Animals ; Anti-Bacterial Agents/*administration&dosage/blood/*pharmacokinetics/urine ; Area Under Curve ; *Buffaloes ; Cefotaxime/*administration&dosage/blood/*pharmacokinetics/urine ; Drug Administration Schedule ; Half-Life ; Male ; Tissue Distribution

The present study aimed to investigate the pharmacokinetic variation of ofloxacin based on gender-related difference in the expression of multidrug resistance-associated protein (Abcc2/Mrp2) in rat kidney. The concentrations of ofloxacin in rat plasma and urine were determined after tail vein administration (30 mg x kg(-1)) by high-performance liquid chromatography (HPLC) method. Expression of Mrp2 in kidney of male and female rats was qualitatively and quantitatively detected by immunohistochemistry and flow cytometry, separately. The results showed that AUC value of ofloxacin was lower in male rats than that in female rats and the total amount of ofloxacin excreted in the urine was higher in male rats than that in female rats. And the expression of Mrp2 in male rat kidney was higher than that in female rats. All results suggested that gender-related differences in pharmacokinetics of ofloxacin may be attributed to the differences in the expression of Mrp2 in kidney of male and female rats.
ATP-Binding Cassette Transporters ; metabolism ; Animals ; Anti-Bacterial Agents ; blood ; pharmacokinetics ; urine ; Area Under Curve ; Female ; Kidney ; metabolism ; Male ; Ofloxacin ; blood ; pharmacokinetics ; urine ; Rats ; Rats, Wistar ; Sex Characteristics

AIMTo establish a new and simple flow injection method for the rapid determination of acetylspiramycin (ASPM).

METHODSASPM was determined by chemiluminescence (CL) method combined with flow injection (FI) technology, which was based on the inhibitive effect of ASPM on the chemiluminescence reaction of the luminol-K3Fe (CN)6 system.

RESULTSThe decrease of chemiluminescence intensity was proportional to the logarithm of ASPM concentration (0.1-100) microgram.L-1, the detection limit was 40 ng.L-1 (3 sigma). The whole process, including sampling and washing, could be completed in 0.5 min with a RSD less than 3.0% (n = 5).

CONCLUSIONThe FI-CL method is of both high sensitivity and good selectivity giving a throughput of 120 h-1. The proposed method was applied successfully to the determination of ASPM in pharmaceutical preparations and human urine without any pre-treatment. It was found that the ASPM concentration reached its maximum after being orally administrated for two hours.

Anti-Bacterial Agents ; analysis ; blood ; urine ; Flow Injection Analysis ; Humans ; Luminescent Measurements ; Luminol ; chemistry ; Male ; Microchemistry ; Spiramycin ; analogs & derivatives ; analysis ; blood ; urine

The pharmacokinetics and urinary excretion following single intramuscular administration of levofloxacin at a dose of 4 mg/kg was investigated in seven male cross bred calves. Appreciable plasma concentration of levofloxacin (0.38 +/- 0.06 microgram/ml) was detected at 1 min after injection and the peak plasma level of 3.07 +/- 0.08 microgram/ml was observed at 1 h. The drug level above MIC(90) in plasma was detected up to 12 h after administration. Rapid absorption of the drug was also evident by the high value of the absorption rate constant (2.14 +/- 0.24 /h). The overall systemic bioavailability of levofloxacin, after intramuscular administration, was 56.6 +/- 12.4%. The high value of AUC (7.66 +/- 0.72 mg.h/ml) reflected the vast area of body covered by drug concentration. Extensive distribution of the drug into various body fluids and tissues was noted by the high value of Vd(area) (1.02 +/- 0.05 l/kg). The high ratio of AUC/MIC (76.6 +/- 7.25) obtained in this study indicated excellent clinical and bacteriological efficacy of levofloxacin in calves. The elimination half-life and MRT were 3.67 +/- 0.4 h and 5.57 +/- 0.51 h, respectively. The total body clearance (Cl(B)) was 204.9 +/- 22.6 ml/kg/h. On the basis of the pharmacokinetic parameters, a suitable intramuscular dosage regimen for levofloxacin in calves would be 1.5 mg/kg repeated at 12 h intervals.
Animals ; Anti-Bacterial Agents/administration & dosage/blood/*pharmacokinetics/urine ; Area Under Curve ; Biological Availability ; Cattle/*metabolism/urine ; Half-Life ; Injections, Intramuscular/veterinary ; Male ; Ofloxacin/administration & dosage/blood/*pharmacokinetics/urine

OBJECTIVE: To develop a method for simultaneous determination of sixteen antibiotics in human urine by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). METHODS: With Piperacillin as an internal standard, the target antibiotics in urine samples were enriched and purified by Oasis HLB solid phase extraction (SPE) cartridges, then separated in a ZORBAX SB-C18 column with a gradient elution of mobile phase of 0.1% formic acid water and acetonitrile, finally analyzed with multiple reaction monitoring (MRM) mode. RESULTS: The limits of detection (LOD) for these sixteen antibiotics were in the range of 0.05-10.0 ng/mL and the limits of quantification (LOQ) in the range of 0.25-20.0 ng/mL. Within the related linear range, the related coefficient (r) of sixteen antibiotics were all more than 0.995. Accuracies for these antibiotics were ranged from 82.0%-119.3%, the within-day precision were less than 13.9%. CONCLUSION The developed method is sensitive, specific and appropriate for the analysis of antibiotics in forensic toxicology and therapeutic drugs monitoring.
Ampicillin/urine* ; Anti-Bacterial Agents/urine* ; Chromatography, High Pressure Liquid/methods* ; Forensic Toxicology ; Humans ; Hydrogen-Ion Concentration ; Penicillins/urine* ; Reproducibility of Results ; Sensitivity and Specificity ; Solid Phase Extraction ; Solvents/chemistry* ; Spectrometry, Mass, Electrospray Ionization/methods* ; Tandem Mass Spectrometry/methods* ; Time Factors

PURPOSE: Recently, many evidence-based guidelines for the management of urinary tract infection (UTI) have been developed because of the importance of proper management. However, there is a lack of data regarding how pediatricians manage UTIs in Korea. Therefore, we surveyed pediatricians to determine whether they manage UTIs in an appropriate manner. METHODS: A postal questionnaire survey of 78 pediatricians practicing in Daegu city was performed. Subjects were asked about diagnosis, imaging studies, treatment, and prevention of UTIs. RESULTS: Most of the respondents (94.8%) performed urinalysis to diagnose UTI in febrile children with an unknown fever focus. However, many preferred inaccurate collection methods, such as bagged urine collection, and did not obtain urine cultures. The most frequently performed imaging modality was renal-bladder ultrasonogram. Orally administered antibiotics were preferred unless admission was needed. After diagnosis of UTI, the pediatricians usually provided information to caregivers about the disease itself and supplementary treatment. Of the respondents, only 28.6% had their own guidelines for management of vesicoureteral reflux. CONCLUSION: Most pediatricians suspected UTI in febrile children with an unknown focus appropriately. Nevertheless, the fact that many pediatricians preferred inaccurate urine collection methods and did not perform sufficient imaging studies to detect associated abnormalities likely resulted in overtreatment due to false-positive diagnosis of UTI and a low probability of ruling out genitourinary anatomical problems. To improve the quality of management of UTI, pediatricians should follow scientific and evidence-based guidelines.
Anti-Bacterial Agents ; Caregivers ; Child ; Surveys and Questionnaires ; Fever ; Humans ; Korea ; Pediatrics ; Primary Health Care ; Surveys and Questionnaires ; Urinalysis ; Urinary Tract ; Urinary Tract Infections ; Urine Specimen Collection

A study of amoxicillin pharmacokinetics was conducted in healthy goats and goats with chronic lead intoxication. The intoxicated goats had increased serum concentrations of liver enzymes (alanine aminotransferase and gamma-glutamyl transferase), blood urea nitrogen, and reactivated delta-aminolevulinic acid dehydratase compared to the controls. Following intravenous amoxicillin (10 mg/kg bw) in control and lead-intoxicated goats, elimination half-lives were 4.14 and 1.26 h, respectively. The volumes of distribution based on the terminal phase were 1.19 and 0.38 L/kg, respectively, and those at steady-state were 0.54 and 0.18 L/kg, respectively. After intramuscular (IM) amoxicillin (10 mg/kg bw) in lead-intoxicated goats and control animals, the absorption, distribution, and elimination of the drug were more rapid in lead-intoxicated goats than the controls. Peak serum concentrations of 21.89 and 12.19 microg/mL were achieved at 1 h and 2 h, respectively, in lead-intoxicated and control goats. Amoxicillin bioavailability in the lead-intoxicated goats decreased 20% compared to the controls. After amoxicillin, more of the drug was excreted in the urine from lead-intoxicated goats than the controls. Our results suggested that lead intoxication in goats increases the rate of amoxicillin absorption after IM administration and distribution and elimination. Thus, lead intoxication may impair the therapeutic effectiveness of amoxicillin.
Amoxicillin/blood/*pharmacokinetics/urine ; Animals ; Anti-Bacterial Agents/blood/*pharmacokinetics/urine ; Area Under Curve ; Chromatography, High Pressure Liquid/veterinary ; Goat Diseases/*chemically induced/metabolism ; Goats ; Half-Life ; Injections, Intramuscular/veterinary ; Injections, Intravenous/veterinary ; Lead Poisoning/etiology/metabolism/*veterinary ; Male

BACKGROUNDA new fluroquinolone antibacterial agent, antofloxacin hydrochloride, developed in China, is an 8-NH(2) derivant of levofloxacin. The purpose of the study was to evaluate the pharmacokinetic characteristics of single and multiple oral doses of antofloxacin hydrochloride in Chinese healthy male volunteers.

METHODSAn open-label, non-randomized, single and multiple dose clinical trial was conducted. In single dose study, 12 subjects took 200 mg antofloxacin hydrochloride. In multiple dose study, 12 subjects took antofloxacin hydrochloride 400 mg once on day 1 and 200 mg once daily from day 2 to day 7. HPLC was used to assay the serum and urinary concentrations of antofloxacin.

RESULTSIn single dose study, the maximum concentration of drug in serum (C(max)), the time to reach C(max) (T(max)), and the area under the serum concentration-time curve (AUC (0-∞)) of antofloxacin were (1.89 ± 0.65) mg/L, (1.29 ± 0.26) hours, and (25.24 ± 7.26) mg×h(-1)×L(-1), respectively. Accumulating elimination rate of antoflocaxin from urine within 120 hours was 39.1%. In multiple dose study, blood concentration of antofloxiacin achieved stable state on day 2 after dosing. The minimum concentration drug in serum (C(min)), AUCss, mean concentration of drug in serum (C(av)), and degree of fluctuation (DF) were (0.73 ± 0.18) mg/L, (47.59 ± 7.85) mg×h(-1)×L(-1), (1.98 ± 0.33) mg/L, and 1.74 ± 0.60, respectively. On day 7 after dosing, T(max), C(max), and AUC (0-∞) was (1.14 ± 0.50) hours, (2.52 ± 0.38) mg/L, and (48.77 ± 8.44) mg×h(-1)×L(-1), respectively. Accumulating elimination rate of antofloxaxin from urine within 120 hours after the last dosing was 60.06%.

CONCLUSIONSThe regimen of 400 mg loading dose given on the first treatment day and then 200 mg dose once daily results in satisfactory serum drug concentration.

Administration, Oral ; Adolescent ; Adult ; Anti-Bacterial Agents ; administration & dosage ; blood ; pharmacokinetics ; urine ; Chromatography, High Pressure Liquid ; Humans ; Levofloxacin ; Male ; Ofloxacin ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics ; urine ; Young Adult

BACKGROUND/AIMS: Efforts to decrease the use of extended-spectrum cephalosporins are required to prevent the selection and transmission of multi-drug resistant pathogens, such as extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae. The objectives of this study were to assess the clinical efficacy of intravenous cefuroxime as an empirical antibiotic for the treatment of hospitalized women with acute pyelonephritis (APN) caused by Escherichia coli. METHODS: We analyzed the clinical and microbiologic database of 328 hospitalized women with community-onset APN. RESULTS: Of 328 women with APN, 22 patients had cefuroxime-resistant E. coli APN, and 306 patients had cefuroxime-susceptible E. coli APN. The early clinical success rates were significantly higher (p = 0.001) in the cefuroxime-susceptible group (90.8%, 278/306) than in the cefuroxime-resistant group (68.2%, 15/22) at 72 hours. The clinical cure rates at 4 to 14 days after completing antimicrobial therapy were not significantly different in the cefuroxime-resistant or -susceptible groups, with 88.2% (15/17) and 97.8% (223/228; p = 0.078), respectively. The microbiological cure rates were not significantly different and were 90.9% (10/11) and 93.4% (128/137), respectively (p =0.550). The median duration of hospitalization in the cefuroxime-resistant and -susceptible groups was 10 days (interquartile range [IQR], 8 to 13) and 10 days (IQR, 8 to 14), respectively (p =0.319). CONCLUSIONS: Cefuroxime, a second-generation cephalosporin, can be used for the initial empirical therapy of community-onset APN if tailored according to uropathogen identification and susceptibility results, especially in areas where the prevalence rate of ESBL-producing uropathogens is low.
Administration, Intravenous ; Aged ; Anti-Bacterial Agents/administration & dosage/adverse effects/*therapeutic use ; Cefuroxime/administration & dosage/adverse effects/*therapeutic use ; Community-Acquired Infections/diagnosis/*drug therapy/microbiology/urine ; Databases, Factual ; *Drug Resistance, Bacterial ; Escherichia coli/*drug effects/isolation & purification ; Escherichia coli Infections/diagnosis/*drug therapy/microbiology/urine ; Female ; Hospitalization ; Humans ; Microbial Sensitivity Tests ; Middle Aged ; Pyelonephritis/diagnosis/*drug therapy/microbiology/urine ; Remission Induction ; Retrospective Studies ; Time Factors ; Treatment Outcome ; Urinalysis ; Urinary Tract Infections/diagnosis/*drug therapy/microbiology/urine ; Urine/microbiology