Pharmacokinetic comparison with different assays for simultaneous determination of cis-,trans-cefprozil diastereomers in human plasma / 药物分析学报

The purpose of this study was to compare pharmacokinetic (PK) parameters obtained using two newly developed assays,HPLC-UV and UPLC-ESI-MS/MS.Selection of assay and results obtained therefrom are very important in PK studies and can have a major impact on the PK-based clinical dose and usage settings.For this study,we developed two new methods that are most commonly used in biosample analysis and focused on PK parameters obtained from them.By HPLC-UV equipped with a Luna-C8 column using UV detector,cefprozil diastereomers were separated using water containing 2％ (V/V) acetic acid and acetonitrile as a mobile phase.By UPLC-ESI-MS/MS equipped with a HALO-C18column,cefprozil diastereomers were separated using 0.5％ (V/V) aqueous formic acid containing 5 mM ammonium-formate buffer and methanol as a mobile phase.Chromatograms showed high resolution,sensitivity,and selectivity without interference by plasma constituents.Both intra-and inter-day precisions (CV,％)were within 8.88％ for HPLC-UV and UPLC-ESI-MS/MS.Accuracy of both methods was 95.67％-107.50％.These two analytical methods satisfied the criteria of international guidance and could be successfully applied to PK study.Comparison of PK parameters between two assays confirmed that there is a dif-ference in the predicted minimum plasma concentrations at steady state,which may affect clinical dose and usage settings.Furthermore,we confirmed possible correlation between PK parameters and various biochemical parameters after oral administration of 1000 mg cefprozil to humans.

Identification of Unknown Impurities in Cefprozil Suspension by LC-HR-MS/MS / 中国药房

OBJECTIVE：To de termine unknown impurities in Cefprozil suspension ，and to identify its structure. METHODS ： LC-HR-MS/MS method was used to detect and identify unknown impurities in Cefprozil suspension. The determination was performed on Thermo HyPURITY TM C18 with mobile phase consisted of acetonitrile- 0.013％ formic acid solution （gradient elution ） at the flow rate of 1.0 mL/min. The detection wavelength was set at 230 nm，and column temperature was 40 ℃. The sample size was 20 μL. ESI+ full scanning was carried out with electrospray ion source scanning range was mass-charge ratio （m/z）100-1 500 with spray voltage of 3.8 kV，metal capillary temperature of 320 ℃，sheath gas pressure of 60 Arb，auxiliary gas pressure of 10 Arb，spray temperature of 280 ℃. RESULTS ：Under this condition ，the detection limit of impurity K was 0.202 μg/mL. RSDs of precision and reproducibility tests were both lower than 4％. Three unknown impurities were found around impurity K ，which were isomers of each other. The retention time of ions were 17.83-19.31 min，and the secondary parent ion were all m/z 436.150 0[M+ H]+，which may be the product of ring opening and dehydration of cefpropene. CONCLUSIONS ：Three unknown impurities near impurity K in Cefprozil suspension were detected by this method.

Study on the Interaction between Cefprozil and Bovine Serum Albumin by Spectrometry / 中国药房

OBJECTIVE:To study the interaction of cefprozil (CE) with bovine serum albumine (BSA). METHODS:Under the temperatures of 289,299 and 309 K,the interaction of CE with BSA for 50 min had been studied by fluorescence quenching, UV spectrometry and synchronous fluorescence spectroscopy. Quenching constant(KSV)and speed constant(Kq)were calculated by Stern-Volmer equation. Static quenching constant(KLB)was obtained by Lineweaver-Burk equation,and UV spectrogram was used to determine the type of quenching. Double logarithmic equation was used to calculate the binding constants (Kb) and the number of binding site(n). Thermodynamic equation was used to obtain ΔH,ΔS,ΔG. Hill's coefficients(nH)was obtained by Hill equa-tion. RESULTS:At three different temperatures,with CE concentration increasing,fluorescence intensity of BSA decreased regular-ly. The value of KSV,Kq,KLB,Kb and n and nH decreased with the temperature increasing. ΔH,ΔS and ΔG were lower than 0. The numbers of binding sites were approximately equal to 1 and nH<1. CONCLUSIONS:CE statically quench the fluorescence of BSA,and the binding of them have been found to certain extent. The process of binding is spontaneous exothermic process. The main binding forces include Hydrogen bonds and Van der Waals forces,and primary binding site for CE is located at sub-domain ⅡA of BSA. There was some negative cooperative effect. CE would not affect the conformation of BSA. The binding site of CE and BSA is near by tyrosine residue.

Terapia ambulatoria con cefprozil en niños con neumonía adquirida en la comunidad / Ambulatory therapy with cefprozil in children with pneumonia acquired in the community

Demostrar que el cefprozil es eficaz y seguro en neumonías adquiridas en la comunidad en edad pediátrica en aquellos casos donde no existan evidencias de complicaciones. Se seleccionaron 30 niños de ambos sexos mayores de 6 meses de edad que cumplieron con los criterios de inclusión, con posibilidades de cumplir el tratamiento en forma ambulatoria, suministrándole el cefprozil a dosis de 50 mg/kg/peso/día por vía oral con controles diarios por un lapso de 7 a 10 días, realizándosele evaluación clínica y examen físico detallados, así como pruebas de laboratorio y cultivos. Predominó el sexo masculino (66,6 por ciento). La mayor incidencia por grupo etario fue entre 6 meses y 5 años de edad, con un promedio de 5 años. La fiebre y la tos estuvieron presentes en 15 de los casos (50 por ciento), el hemograma mostró leucocitosis con neutrofilia y positividad de la VSG y PCR en el 50 por ciento de los casos. El hemocultivo fue positivo para Streptococcus pneumoniae (3 = 10 por ciento) y Moraxella catarralis (1 = 3,33 por ciento), siendo negativos en un 86.66 por ciento. El hallazgo radiológico reveló infiltrado intersticial difuso bilateral (22 = 73,33 por ciento) y focos de consolidación (8 = 26,66 por ciento). El fármaco mostró seguridad y eficacia en el 93,33 por ciento de los casos y no se evidenció efectos colaterales. La terapia con cefprozil en NAC en edad pediátrica demostró eficacia terapéutica sin efectos adversos y con beneficios clínicos y económicos tanto para el paciente como para los padres. Asimismo, la terapia con cefprozil en NAC representa una alternativa eficaz en tratamientos ambulatorios por vía oral y disminuye la masificación en hospitalizaciones innecesarias.

Preparation and Quality Control of Taste-masked Cefprozil Dry Suspension / 中国药房

OBJECTIVE:To prepare taste-masked cefprozil dry suspension and establish its quality control method. METHODS: The suspension was prepared with glyceryl monostearin used as taste-masked agent and cefprozil as principal agent. The content of cefprozil was determined by HPLC,meanwhile the dissolution rate of the preparation was determined. RESULTS: The preparation was off-white or yellowish granula and it was up to the relative standard specified in Chinese Pharmacopeia (2005 edition) in inspection. The linear ranges of cis-isomer and trans-isomer of cefprozil were 0.05～0.5 mg?mL-1(r=0.999 9) and 5.0～50 ?g?mL-1(r=0.999 9),respectively. The average recoveries were 99.7%(RSD=0.32%,n=6) and 100.7% (RSD=0.23%,n=6),respectively. The preparation had a good taste and its dissolution rate within 45 minutes was as high as about 100%. CONCLUSIONS: The taste-masked cefprozil dry suspension has been successfully prepared by this method mentioned above;furthermore,the quality indexes of the suspension are up to the standard.

Causative Pathogens and Therapeutic Assessment of Cefprozil in Acute Otitis Media

PURPOSE: AOM is the most common bacterial URI in children. The bacteriology and antibiotic Tx of AOM in children has been studied in many countries. But, there is few study of causative pathogens and antibiotic Tx of AOM in our country. In this aspect, we performed prospective clinical study to confirm the causative pathogens and assess the clinical responses of cefprozil in AOM patients. METHODS: Thirty three AOM patients enrolled in this study. Tympanocentesis for isolation of causa tive pathogens were performed before Tx of cefprozil. The study patients received cefprozil with dose of 15 mg/kg/bid.po/day for 10-12 days, and initially assessed the clinical response at 4-5 days after receiving cefprozil and finally at the end visit. In vitro susceptibility tests of cefprozil to isolated pathogens were done by disc diffusion method, and in vitro susceptibility tests of cefaclor and cefixime to isolated pathogens were simultaneously performed. RESULTS: Bacterial pathogens[S. pneumoniae(10), H. influenzae(5), S. aureus(2), M. catarrhalis(1) and Group A stretococcus(1)] were isolated from 19 patients. Clinically, all patients had history of abrupt high fever except one. Tympanic perforation was dominant in pathogens isolated cases, and otalgia was significantly developed in non-pathogens isolated cases. The ages of pathogens isolated cases were usually below 2 years. Eighty four point nine percent of the patients including two cases with isolation of intermediate resistant S. pneumoniae were clinically improved. Antimicrobial in vitro activity to S. pneumoniae of cefprozil were superior than that of cefacor and cefixime. CONCLUSION: We confirm that bacteria has the causative role in about 60% cases, and S. pneumoniae is the most common pathogen. Clinically, there were some differences in symptoms, signs and ages between pathogens isolated and non-pathogens isolated cases. The clinical responses of cefprozil in our patients revealed similar outcomes to other countries. And we reconfirm that cefprozil may be clinically effective in cases of AOM due to intermediate resistant S. pneumoniae.

Penetration of Cefprozil into Middle Ear Effusion in Pediatric Chronic Otitis Meida with Effusion / 대한이비인후과학회지

BACKGROUND: From a pharmacokinetic standpoint, middle ear effusion (MEE) acts as a sequestered compartment since diffusion of antibiotics from serum and to this compartment is limited. The effectiveness of an antibiotic to eradicate infection within an anatomic compartment is related to both its ability to penetrate and the susceptibility of the causative pathogen. OBJECTIVE: The goal of this study was to determine the steady state plasma and MEE concentrations of cefprozil in pediatric chronic otitis media with effusion (COME). MATERIALS AND METHODS: Twenty-five children with COME were enrolled, and MEE was collected using a ventilation tube insertion after 0.5, 2, 3, 5, and 6 hours of single oral administration of 15 mg Cefprozil/kg body weight. Blood samples were also collected as soon as the MEE was collected, and analyzed in order to measure the concentration of Cefprozil using the validated high performance liquid chromatography (HPLC) method. RESULTS: The mean concentrations of cefprozil in MEE ranged from 0.4 to 4.4 ug/ml. The penetration of cefprozil into the MEE was rapid and effectively. Cefprozil in the MEE was maintained at a greater level than MIC90 in Streptococcus pneumoniae for at least 6 hours after administration of 15mg/kg. CONCLUSION: Cefprozil penetrates well into MEE in patients with pediatric COME.