Fiber-Enhanced Raman Sensing of Cefuroxime in Human Urine.

Fiber-enhanced Raman spectroscopy was developed for the chemically selective and sensitive quantification of the important antibiotic cefuroxime in human urine. A novel optical sensor fiber was drawn and precisely prepared. In this fiber structure, light is strongly confined in the selectively filled liquid core, and the Raman scattered signal is collected with unprecedented efficiency over an extended interaction length. The filling, emptying, and robustness are highly improved due to the large core size (>30 µm). Broadband step-index guidance allows the free choice of the most suitable excitation wavelength in complex body fluids. The limit of detection of cefuroxime in human urine was improved by 2 orders of magnitude (to µM level). The quantification of cefuroxime was achieved in urine after oral administration. This method has great potential for the point-of-care monitoring of antibiotics concentrations and is an important step forward to enable clinicians to rapidly adjust doses.

First-derivative spectrophotometric and LC determination of cefuroxime and cefadroxil in urine.

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.

The renal clearance of cefuroxime and ceftazidime and the effect of probenecid on their tubular excretion.

1. The renal tubular excretion of cefuroxime and ceftazidime in relation to the coadministration of probenecid was investigated in eight and two healthy subjects, respectively. 2. Cefuroxime or ceftazidime were administered by i.v. infusion and 1 g probenecid was administered orally after steady state plasma concentrations of the cephalosporin were reached. 3. In a second session the same antibiotic was administered at increasing infusion rates such that three different levels of plasma drug concentration were achieved. 4. The renal clearance of antibiotic was calculated based upon unbound plasma concentration, and tubular clearance was estimated by subtracting inulin clearance from the renal clearance of the antibiotic. 5. Non-linear regression analysis was used to estimate parameters describing the saturability of tubular excretion and the effect of probenecid inhibition, i.e. EC50 and Rtub,max, could be established for cefuroxime: EC50 was 248 (s.d. 130) mg l-1 and Rtub,max was 1.852 (s.d. 0.577) mg h-1. Tubular excretion of ceftazidime was practically zero. The EC50 of probenecid for inhibition of the tubular excretion of cefuroxime was 0.80 (s.d. 0.31) mg l-1. 6. The results indicate that in the therapeutic plasma concentration range of cefuroxime its renal clearance is not saturated. Probenecid at therapeutic doses will block tubular excretion of cefuroxime almost completely.

The effect of cefuroxime axetil on the faecal flora of healthy volunteers.

The effect on the faecal flora of cefuroxime axetil, an oral ester of cefuroxime, was examined in ten healthy volunteers following a dose of 250 mg twice a day for 41/2 days. The mean blood concentration 2 h after the ninth dose was 3.6 mg/l and the urinary excretion was approximately 40% in 6 h and 50% in 24 h. Two volunteers developed mild diarrhoea and one candida vaginitis. Although there was variation between volunteers in the changes found in the faecal flora, the major effects were a reduction in the total anaerobic bacterial count, particularly where high levels of cefuroxime were present in the faeces and a significant decrease or elimination of strains of Enterobacteriaceae plus an increase in the streptococcal count. Six volunteers showed an increase in the candida count. Clostridium difficile was not isolated from any volunteer and toxin was not present in the two volunteers who developed diarrhoea. Four volunteers showed high levels of cefuroxime in the faeces on the fourth or fifth days of treatment.

Effect of dose and food on the bioavailability of cefuroxime axetil.

Cefuroxime axetil is an ester pro-drug which permits the oral administration of cefuroxime. This study was designed to evaluate the dose proportionality of four different doses administered after a meal and to determine the absolute bioavailability of cefuroxime axetil administered with and without food. The study was a six-way randomized crossover trial in 12 normal male volunteers. Subjects received an intravenous dose of cefuroxime (500 mg) and five oral doses of cefuroxime axetil (125, 250, 500-twice, 1000 mg). The intravenous dose and one of the 500 mg doses was administered after an overnight fast. The other four oral doses were administered after a standard meal. Blood samples were collected prior to each dose and serially for 12 h after the dose. Urine was collected for 24 h. Plasma and urine samples were analysed for cefuroxime by high pressure liquid chromatography. There was a linear relationship between the fed dose and both the area under the plasma concentration time curve (r2 = 0.958) and the peak plasma concentration (r2 = 0.943). Based on a comparison of the AUC for the oral and intravenous data, 36 per cent of the fasting and 52 per cent of the fed 500 mg doses were absorbed. The mean peak plasma concentration was 43 per cent greater after the fed dose than the fasting dose. A plot of the mean fraction of unabsorbed drug versus time reveals that absorption is an apparent zero order process from 0.5 to 3 h after dosing.

Cefuroxime in CMW bone cement. A clinical study.

This paper presents the results of adding the antibiotic cefuroxime to CMW bone cement in a group of patients undergoing total hip or knee replacement, in which the levels of cefuroxime were assayed in the blood, wound drainage fluid, urine and surplus bone cement. It was found that very small amounts of cefuroxime, less than 5%, were recovered in the urine, serum and drainage fluid in the first week following operation, and since it is known that cefuroxime is not metabolised or excreted elsewhere in the body, it must follow that approximately 95% remains in the bone cement as a potential source of prophylaxis against infection.

Pharmacokinetics of cefuroxime in pregnancy.

Most pharmacokinetic studies of antibodies in pregnancy have been carried out at the time of abortion or delivery. Whether such data represent pregnancy as such is not known. The present study compares the pharmacokinetic properties of cefuroxime in seven women during pregnancy, at delivery, and after delivery. After intravenous administration of 750 mg of cefuroxime, levels of the drug in plasma and urine were measured during a period of 8 hours. Levels of cefuroxime in cord plasma and amniotic fluid were registered, as were levels of plasma from the neonates at 6 and 12 hours. Plasma levels were significantly lower during pregnancy than afterward, drug half-life was significantly shorter, and clearance and recovery in urine were significantly higher. Differences, although less consistent, were observed in certain parameters at delivery, as compared to earlier in pregnancy, thus indicating that pharmacokinetic data obtained at delivery may not be typical of pregnancy as such. Passage of cefuroxime across the placenta was well demonstrable in all cases.

Fluorimetric determination of cefuroxime in body fluids.

A simple and accurate fluorimetric procedure for measuring cefuroxime in body fluids is described. A fluorescent product was produced by addition of hydrochloric acid, heating, and cooling, followed by addition of sodium hydroxide and further heating at 100 degree C. The fluorescence intensity of the final solution was measured in a fluorimeter at an excitation wavelength of 375 nm and an emission wavelength of 440 nm and related to the antibiotic concentration. Thin-layer chromatography of the final solution showed a single fluorescent spot (Rf value, 0.6). Freedom from interference from other therapeutic agents and endogenous substances, as well as the close correlation between this method and the standard microbiological assay method, was demonstrated. The simplicity and reliability of the fluorimetric assay method make it particularly suitable for clinical use.

[Clinical study in cefuroxime in pediatric field (author's transl)].

Cefuroxime (CXM), a new cephalosporin antibiotic, was used in pediatric field, and the following results were obtained. 1. Absorption and excretion CXM was administered by intravenous drip infusion to 3 patients aged 14 years, 1 year and 1 month, and 5 years and 3 months, respectively, at doses of 15.4 mg/kg, 14.1 mg/kg, and 13.2 mg/kg. The following blood levels were obtained; 71 micrograms/ml at the completion of infusion, 26.8 micrograms/ml at 30 minutes, 13.2 micrograms/ml at 1 hours, 5.05 micrograms/ml at 2 hours, 2.07 micrograms/ml at 4 hours, and less than 0.45 micrograms/ml at 6 hours after the infusion. Urinary excretion of the drug administered was measured in one of these cases. The urinary excretion rate at 1 approximately 6 hours after intravenous drip infusion was 50.4%. 2. Clinical result CXM 17 approximately 55 mg/kg were administered for 2 approximately 4 days to 6 patients with acute respiratory tract infection, 1 with acute cervical lymphadenitis, and 1 with acute enteritis. The clinical results was poor in the case with acute enteritis and good in the other 7 cases. No side effect was observed in 9 cases (the above 8 cases plus 1 unassessable case), and the laboratory examination results showed no abnormality, either.