Preconcentration and determination of ceftazidime in real samples using dispersive liquid-liquid microextraction and high-performance liquid chromatography with the aid of experimental design.

A rapid and simple method for the extraction and preconcentration of ceftazidime in aqueous samples has been developed using dispersive liquid-liquid microextraction followed by high-performance liquid chromatography analysis. The extraction parameters, such as the volume of extraction solvent and disperser solvent, salt effect, sample volume, centrifuge rate, centrifuge time, extraction time, and temperature in the dispersive liquid-liquid microextraction process, were studied and optimized with the experimental design methods. Firstly, for the preliminary screening of the parameters the taguchi design was used and then, the fractional factorial design was used for significant factors optimization. At the optimum conditions, the calibration curves for ceftazidime indicated good linearity over the range of 0.001-10 µg/mL with correlation coefficients higher than the 0.98, and the limits of detection were 0.13 and 0.17 ng/mL, for water and urine samples, respectively. The proposed method successfully employed to determine ceftazidime in water and urine samples and good agreement between the experimental data and predictive values has been achieved.

Study on the resonance Rayleigh scattering spectra of the interactions of palladium (II)-cephalosporins chelates with 4,5-dibromofluorescein and their analytical applications.

In pH 2.8-3.8 BR buffer medium, the third generation cephalosporin antibiotics (TGCs) such as ceftazidime (CZD), ceftriaxone (CTRX), cefoperazone (CPZ), and cefotaxime (CFTM) react with palladium(II) (Pd(II)) to form 1:2 yellowish-brown cationic chelates, which further react with 4,5-dibromofluorescein (DBF) to form 1:3 brown ion-association complexes. As a result, not only the spectra of absorption and fluorescence are changed, but also the resonance Rayleigh scattering (RRS) is enhanced greatly and the new RRS spectra are observed. The four TGCs products have similar spectral characteristics and their maximum RRS wavelengths are all located at 291 nm. The quantitative determination ranges and the detection limits of the four TGCs are 0.0065-1.0 microg mL(-1) and 2.0 ng mL(-1) for CZD, 0.0070-1.1 microg mL(-1) and 2.2 ng mL(-1) for CTRX, 0.0090-1.6 microg mL(-1) and 2.7 ng mL(-1) for CPZ, and 0.014-2.2 microg mL(-1) and 4.2 ng mL(-1) for CFTM, respectively. The optimum conditions of the reactions and the effects of foreign substances are investigated, and the composition of ion-association complexes is discussed also. Based on the ion-association reaction, a highly sensitive, simple and rapid method has been proposed to the determination of TGCs.

Pharmacokinetic interactions of ceftazidime, imipenem and aztreonam with amikacin in healthy volunteers.

The common usage of extended spectrum beta-lactams co-administered with amikacin in everyday clinical practice for infections by multidrug-resistant isolates has created the need to search for pharmacokinetic interaction. Eighteen healthy volunteers were enrolled in the study; six were administered 1g of ceftazidime singly intravenously or combined with 0.5 g of amikacin; six received 0.5 g of imipenem singly or combined with 0.5 g of amikacin and six 1g of aztreonam singly or combined with 0.5 g of amikacin. Blood and urine samples were collected at regular time intervals and apparent serum levels were determined by a microbiological assay. Co-administration of ceftazidime and amikacin resulted in higher C(max) and AUC for amikacin than when administered alone. Co-administration of imipenem and amikacin resulted in higher C(max) for imipenem than when administered alone. The tested interactions did not affect plasma half-life (t(1/2)) and clearance rate of any antimicrobial compared with its single administration. All tested drugs were mainly eliminated by glomerular filtration. It is concluded that co-administration of ceftazidime, imipenem or aztreonam with amikacin in healthy volunteers might affect C(max) and AUC without influencing any other pharmacokinetic parameter. The probable clinical endpoint is that giving ceftazidime, imipenem or aztreonam with amikacin might result in a transient elevation of beta-lactam serum levels without further affecting the complete pharmacokinetic profile of each drug as obtained after administration of the drug alone.

Spectrophotometric methods for the determination of cephradine or ceftazidine in human urine using batch and flow-injection procedures.

Sensitive and fast spectrophotometric methods for the determination of cephradine or ceftazidine in human urine, based on the formation of compounds between these drugs and Pd(II), are described. In the batch procedures the calibration graphs resulting from the measurement of the absorbance at 330 nm is linear over the range 5.0-60.0 micrograms. ml-1 for cephradine and 3.0-60.0 micrograms ml-1 for ceftazidine. The methods were successfully adapted to FI-systems, the peak heights being proportional to cephalosporin concentration over the range 5.0-60.0 micrograms ml-1 for cephradine and 3.0-60.0 micrograms ml-1 for ceftazidine. The sampling frequency was 60 h-1 with a sample injection of 72 microliters.

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.

Comparative study of pharmacokinetics and serum bactericidal activities of cefpirome, ceftazidime, ceftriaxone, imipenem, and ciprofloxacin.

We compared the pharmacokinetics and the serum bactericidal activities of cefpirome, ceftazidime, ceftriaxone, imipenem, and ciprofloxacin. Fifteen healthy volunteers received 1 g of cefpirome, ceftazidime, and ceftriaxone intravenously, 500 mg of imipenem-cilastatin intravenously, and 500 mg of ciprofloxacin orally. High-performance liquid chromatographic assays were used to quantitate unchanged antibiotic in plasma and urine. Serum bactericidal activities were determined against six clinical isolates each of Staphylococcus aureus, Enterobacter cloacae, and Pseudomonas aeruginosa by using a modified microdilution method of Reller and Stratton (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977). Overall, cefpirome exhibited pharmacokinetics similar to those of ceftazidime: half-life (t1/2), 1.95 h; concentration at 1 h (C1h), 47 to 49 micrograms/ml for both antibiotics. Ceftriaxone displayed the longest t1/2 (7.65 h) and the highest C1h (137.8 micrograms/ml), while we observed the shortest t1/2 (1.05 h) and the lowest C1h (19.85 micrograms/ml) with imipenem. At 1 h, cefpirome and, even more so, imipenem showed significantly better serum bactericidal activities against S. aureus (1:273 and 1:80) than did the other antibiotics (P less than 0.0005; analysis of variance with randomized block design and Bonferroni correction). Against E. cloacae, we observed the highest serum bactericidal titers at 1 h with cefpirome, and this superiority vis-à-vis the other antibiotics tested was maintained for up to 8 h after dosing. Ceftazidime remained the most active agent tested against P. aeruginosa (serum bactericidal activity titers, 1:43 at 1 h) up to 8 h. In summary, the study showed that cefpirome and imipenem provide more potent serum bactericidal activities than do broad-spectrum cephalosporins against S. aureus; thus, both of these antibiotics should be adequate against serious S. aureus infections. In addition, cefpirome appears to be a promising alternative for treatment of infections caused by E. cloacae and P. aeruginosa.

[Study on CAZ levels in serum, urine and myocardial tissue during and after open-heart surgery with cardiopulmonary bypass].

Ceftazidime (CAZ) was administered to 10 patients who underwent open heart surgery using an artificial heart and lung (AHL), and the concentrations of the drug in the blood, urine, filtrate and cardiac muscle were measured. Following anesthesia induction, patients were injected intravenously with 2 g CAZ, and then 2 g CAZ was injected initially into the filling solution of the AHL followed by 1 g every 1 hr. After the surgery, patients received 1 g CAZ intravenously followed by the same dose every 12 hr till Day 5 of the surgery. Results obtained were as follows: 1) The concentration of CAZ in the cardiac muscle averaged 41.2 +/- 12.3 micrograms/g, and the ratio to the concentration in the plasma averaged 0.61 +/- 0.12, being considered to be reasonable. 2) The change in the mean plasma concentration of CAZ during extracorporeal circulation was maintained within the range of 109.7 to 337.0 micrograms/ml, and the concentration increased slightly with the repeated injection. In 2 cases, the plasma concentration was transiently more than 400 micrograms/ml, however, no side effect was observed. 3) The mean plasma concentration of CAZ after surgery attained 214.4 +/- 38.9 micrograms/ml, and half-time averaged 2.8 hr. 4) The excretion rates of CAZ in urine and filtrate by the termination of the extracorporeal circulation were 30.6 and 5.2%, respectively, thus the excretion of the drug in filtrate was lower than that in urine. The total excretion rate in both urine and filtrate for 6 hr after surgery was 55.3%. 5) Neither postoperative infection nor side effect were observed in all cases. CAZ is considered to be a useful antibiotics in the cardiac surgery management.

Assay of ceftazidime in biological fluids using high-pressure liquid chromatography.

An HPLC method for the assay of ceftazidime in plasma and urine is described. It is sensitive, accurate and reproducible; results show good agreement with those obtained using microbiological assay.