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Uday B. Kompella - One of the best experts on this subject based on the ideXlab platform.
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development and in vitro evaluation of sustained release poloxamer 407 p407 gel formulations of Ceftiofur
Journal of Controlled Release, 2002Co-Authors: Lin Zhang, Christine Navarre, Daniel L Parsons, Uday B. KompellaAbstract:The objective of this study was to develop sustained release Poloxamer 407 (P407) gel formulations of Ceftiofur for treating foot infections in cattle. The formulations contained 25-35% (w/v) P407 alone or with polyvinyl pyrrolidone (PVP), carboxy methylcellulose (CMC), or hydroxylpropyl methylcellulose (HPMC) as an additive. The in-vitro release profiles of Ceftiofur from the P407 formulations and the gel dissolution profiles were obtained simultaneously. Ceftiofur release followed zero order kinetics and correlated well with the weight percentage of P407 dissolved, indicating that the overall rate of release of Ceftiofur is controlled by dissolution of the P407. An increase in P407 content from 25 to 35% resulted in a decrease in the rate of Ceftiofur release. However, it appears that other factors may have also affected the drug release rate. Inclusion of PVP, CMC, and HPMC in the gel decreased the rate of release of Ceftiofur to some extent. A decrease in the temperatures of the release medium decreased the release rate of Ceftiofur, but not the rate of gel dissolution. The pH of the release medium showed a very slight effect on the release of Ceftiofur and did not affect gel dissolution due to the non-ionic nature of P407.
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Ceftiofur distribution in plasma and joint fluid following regional limb injection in cattle.
Journal of veterinary pharmacology and therapeutics, 1999Co-Authors: Christine Navarre, L Zhang, G Sunkara, S. H. Duran, Uday B. KompellaAbstract:The objective of this study was to evaluate the efficacy of regional intravenous (i.v.) injection of Ceftiofur in delivery of this drug to joint fluid and plasma in a limb distal to a tourniquet in five, healthy, adult, mixed breed beef cattle. A tourniquet was positioned in the mid-metacarpal region, and 500 mg of Ceftiofur was administered through a catheter in the dorsal common digital vein (DCDV). Plasma samples were collected from the catheter at 15, 30 and 45 min postinjection, and from the abaxial proper palmar vein (APPV) at 15 min postinjection. Synovial fluid was collected from the metacarpal phalangeal joint at 45 min postinjection. Ceftiofur concentrations were estimated in plasma and synovial fluid using high-pressure liquid chromatography (HPLC) and a microbiological assay utilizing Pasteurella haemolytica as the test organism. Both assays indicated highest plasma concentrations of Ceftiofur at 15 min, with the concentrations declining with time. Concentrations of Ceftiofur in plasma obtained from the DCDV were not significantly different from APPV levels, indicating rapid distribution of Ceftiofur within the limb. Microbiological assay always demonstrated higher concentrations of Ceftiofur compared with HPLC assay, because the former probably also detected the active metabolites of Ceftiofur as well as the parent compound. At 45 min, Ceftiofur concentrations determined by HPLC were 251+/-97 and 15+/-5 microg/mL in plasma and synovial fluid, respectively. Regional intravenous injection appears to be a feasible technique to produce rapid distribution of Ceftiofur within the limb well above therapeutic concentrations.
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Influence of pH and Temperature on Kinetics of Ceftiofur Degradation in Aqueous Solutions
The Journal of pharmacy and pharmacology, 1999Co-Authors: Gangadhar Sunkara, Christine Navarre, Uday B. KompellaAbstract:The objective of this study was to evaluate the stability of Ceftiofur (1 mg mL(-1)) in aqueous solutions at various pH (1, 3, 5, 7.4 and 10) and temperature (0, 8, 25, 37 and 60 degrees C) conditions. The ionic strength of all these solutions was maintained at 0.5 M. Ceftiofur solutions at pH 5 and 7.4 and in distilled water (pH = 6.8) were tested at all the above temperatures. All other solutions were tested at 60 degrees C. Over a period of 84 h, the stability was evaluated by quantifying Ceftiofur and its degradation product, desfuroylCeftiofur, in the incubation solutions. HPLC was used to analyse these compounds. At 60 degrees C, the rate of degradation was significantly higher at pH 7.4 compared with pH 1, 3, 5 and distilled water. At both 60 degrees C and 25 degrees C, degradation in pH 10 buffer was rapid, with no detectable Ceftiofur levels present at the end of 10 min incubation. Degradation rate constants of Ceftiofur were 0.79+/-0.21, 0.61+/-0.03, 0.44+/-0.05, 1.27+/-0.04 and 0.39+/-0.01 day(-1) at pH 1, 3, 5, 74 and in distilled water, respectively. Formation of desfuroylCeftiofur was the highest (65%) at pH 10. The rate of degradation increased in all aqueous solutions with an increase in the incubation temperature. At pH 7.4 the degradation rate constants were 0.06+/-0.01, 0.06+/-0.01, 0.65+/-0.17, and 1.27+/-0.05 day(-1) at 0, 8, 25, 37 and 67 degrees C, respectively. The energy of activation for Ceftiofur degradation was 25, 42 and 28 kcal mol(-1) at pH 5, 7.4 and in distilled water, respectively. DesfurylCeftiofur formation was the greatest at alkaline pH compared with acidic pH. Ceftiofur degradation accelerated the most at pH 7.4 and was most rapid at pH 10. The results of this study are consistent with rapid clearance of Ceftiofur at physiological pH.
Wolfgang Heuwieser - One of the best experts on this subject based on the ideXlab platform.
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Determination of Ceftiofur derivatives in serum, endometrial tissue, and lochia in puerperal dairy cows after subcutaneous administration of Ceftiofur crystalline free acid
Journal of dairy science, 2011Co-Authors: T.s. Witte, Michael Iwersen, T Kaufmann, Peter Scherpenisse, Aldert A. Bergwerff, Wolfgang HeuwieserAbstract:Abstract Puerperal uterine infections are often associated with decreased reproductive performance in dairy cows. Routine treatment protocols include the systemic administration of antibiotics. Antibiotic drugs, however, should be administered daily over at least 5 d. The objective of this study was to determine concentrations of Ceftiofur derivatives in serum, endometrial tissue, and lochia after subcutaneous administration of Ceftiofur crystalline free acid in 6 clinically healthy puerperal dairy cows with normal parturition. Samples were taken immediately before treatment, 2h after, and then every 24h over a 7-d period. Concentrations of Ceftiofur derivatives were quantified using an HPLC assay. In serum and endometrial tissue, Ceftiofur derivatives could be detected above the reported minimum drug concentrations required to inhibit relevant pathogens such as Escherichia coli and Arcanobacterium pyogenes over a 7-d period. Concentrations of desfuroylCeftiofuracetamide at 5 d after administration of Ceftiofur crystalline free acid were 1.21±0.61 μg/mL in serum, 0.86±0.61 μg/mg in endometrial tissue, and 0.96±1.15 μg/mL in lochia. In lochia, mean concentrations of Ceftiofur derivatives also remained above the minimal inhibitory concentration of relevant pathogens, but showed greater variations between cows.
W Heuwieser - One of the best experts on this subject based on the ideXlab platform.
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randomized controlled clinical trial on the efficacy of nonsteroidal antiinflammatory drugs for the treatment of acute puerperal metritis in dairy cows
Journal of Dairy Science, 2016Co-Authors: A Pohl, S Bertulat, S Borchardt, O Burfeind, W HeuwieserAbstract:The objective of this study was to assess the efficacy of ketoprofen compared with Ceftiofur hydrochloride for the treatment of acute puerperal metritis (APM). Specifically, we set out to compare the incidence of extended treatment (extT) between treatment groups, to determine the prevalence of purulent vaginal discharge (PVD) and milk yield on the first 3 milk tests postpartum, and to analyze reproductive performance of cows treated with ketoprofen or Ceftiofur. Cows with rectal temperature ≥39.5°C and reddish-brown fetid vaginal discharge within the first 10 d in milk (DIM) were diagnosed with APM. Day of enrollment and first day of treatment was considered study day 1. Rectal temperature was recorded daily until study day 7. A total of 610 dairy cows with APM were enrolled in this randomized clinical trial. Cows meeting the inclusion criteria were allocated to treatment with ketoprofen (3mg/kg of body weight, n=300) or treatment with Ceftiofur (1mg/kg of body weight, n=310) on study days 1, 2, and 3. Cows that showed rectal temperature ≥39.5°C between study days 4 and 7 received an extT with Ceftiofur for 3 (ketoprofen group) or 2 (Ceftiofur group) more days. Cows were examined with the Metricheck device (Simcro, Hamilton, New Zealand) between DIM 21 and 40, and vaginal discharge was categorized on a 5-point scale according to the presence of pus. Cows with a score ≥2 were classified as having PVD. Fifty-two cows (35 from ketoprofen group, 17 from Ceftiofur group) were excluded from analysis due to missing protocol compliance (n=37) or concurrent disease (n=15). Cows treated with ketoprofen were more likely to have an extT than cows treated with Ceftiofur (61 vs. 31%). Prevalence of PVD did not differ between the 2 treatment groups (ketoprofen, 56%; Ceftiofur, 53%). Cows, however, that needed an extT after the initial 3-d treatment were more likely to develop PVD than cows without extT (64 vs. 46%). Treatment group did not affect milk yield (ketoprofen group, 35.5±0.4kg; Ceftiofur group, 35.2±0.3kg), first artificial insemination pregnancy risk (ketoprofen group, 20% vs. Ceftiofur group, 25%), median days to first artificial insemination [ketoprofen group, 73 d, 95% confidence interval (CI): 70-75 d vs. Ceftiofur group, 75 d, 95% CI: 72-76 d] and median days to pregnancy (ketoprofen group, 144 d, 95% CI: 132-158 d vs. Ceftiofur group, 133 d, 95% CI: 119-153 d). These results indicate that although cows initially treated with ketoprofen were more likely to receive extT, fewer doses of Ceftiofur (1.83) were required compared with cows initially treated with Ceftiofur (3.63). Moreover, the prevalence of PVD was not increased and milk yield and reproductive performance were not negatively affected by the initial treatment with ketoprofen.
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Ceftiofur derivatives in serum uterine tissues cotyledons and lochia after fetal membrane retention
Journal of Dairy Science, 2006Co-Authors: M Drillich, Peter Scherpenisse, Aldert A. Bergwerff, S Arlt, S Kersting, W HeuwieserAbstract:Abstract The objective of the study was to determine concentrations of Ceftiofur derivatives after subcutaneous application of Ceftiofur hydrochloride in cows with retained fetal membranes. Concentrations of Ceftiofur derivatives detected as desfuroylCeftiofuracetamide were determined in blood serum, endometrium, caruncles, cotyledons, and lochia during 72h. After induction of parturition, 2 primiparous and 4 multiparous cows having retained fetal membranes for at least 12h were studied. All cows received 3 consecutive injections (C1 to C3; 24h apart) of 1-mg Ceftiofur equivalents per kilogram of body weight as Ceftiofur hydrochloride sterile suspension. Samples of blood, endometrium, caruncles, cotyledons, and lochia were collected immediately before each injection (0h) and again at 4, 12, and 24h after C1, C2, and C3. Blood samples were collected from coccygeal vessels. Caruncles were removed from the uterine lumen by manual extirpation and separated from cotyledons. Endometrial tissue (0.5g) was collected by using Kenny's biopsy apparatus. For all samples, concentrations of potentially active Ceftiofur derivatives were quantified using an HPLC assay. Within 2h (serum), 4h (endometrium), and 12h (caruncles, cotyledons, lochia) after C1 and during the entire study period, mean concentration of Ceftiofur derivatives exceeded the reported minimum drug concentrations required to inhibit the growth of 90% of isolates for relevant bacteria such as Escherichia coli, Fusobacterium necrophorum, and Arcanobacterium pyogenes. Only in single samples did concentrations decrease temporarily below the reported minimum drug concentrations required to inhibit the growth of 90% of isolates.
Peter Scherpenisse - One of the best experts on this subject based on the ideXlab platform.
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Determination of Ceftiofur derivatives in serum, endometrial tissue, and lochia in puerperal dairy cows after subcutaneous administration of Ceftiofur crystalline free acid
Journal of dairy science, 2011Co-Authors: T.s. Witte, Michael Iwersen, T Kaufmann, Peter Scherpenisse, Aldert A. Bergwerff, Wolfgang HeuwieserAbstract:Abstract Puerperal uterine infections are often associated with decreased reproductive performance in dairy cows. Routine treatment protocols include the systemic administration of antibiotics. Antibiotic drugs, however, should be administered daily over at least 5 d. The objective of this study was to determine concentrations of Ceftiofur derivatives in serum, endometrial tissue, and lochia after subcutaneous administration of Ceftiofur crystalline free acid in 6 clinically healthy puerperal dairy cows with normal parturition. Samples were taken immediately before treatment, 2h after, and then every 24h over a 7-d period. Concentrations of Ceftiofur derivatives were quantified using an HPLC assay. In serum and endometrial tissue, Ceftiofur derivatives could be detected above the reported minimum drug concentrations required to inhibit relevant pathogens such as Escherichia coli and Arcanobacterium pyogenes over a 7-d period. Concentrations of desfuroylCeftiofuracetamide at 5 d after administration of Ceftiofur crystalline free acid were 1.21±0.61 μg/mL in serum, 0.86±0.61 μg/mg in endometrial tissue, and 0.96±1.15 μg/mL in lochia. In lochia, mean concentrations of Ceftiofur derivatives also remained above the minimal inhibitory concentration of relevant pathogens, but showed greater variations between cows.
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Ceftiofur derivatives in serum uterine tissues cotyledons and lochia after fetal membrane retention
Journal of Dairy Science, 2006Co-Authors: M Drillich, Peter Scherpenisse, Aldert A. Bergwerff, S Arlt, S Kersting, W HeuwieserAbstract:Abstract The objective of the study was to determine concentrations of Ceftiofur derivatives after subcutaneous application of Ceftiofur hydrochloride in cows with retained fetal membranes. Concentrations of Ceftiofur derivatives detected as desfuroylCeftiofuracetamide were determined in blood serum, endometrium, caruncles, cotyledons, and lochia during 72h. After induction of parturition, 2 primiparous and 4 multiparous cows having retained fetal membranes for at least 12h were studied. All cows received 3 consecutive injections (C1 to C3; 24h apart) of 1-mg Ceftiofur equivalents per kilogram of body weight as Ceftiofur hydrochloride sterile suspension. Samples of blood, endometrium, caruncles, cotyledons, and lochia were collected immediately before each injection (0h) and again at 4, 12, and 24h after C1, C2, and C3. Blood samples were collected from coccygeal vessels. Caruncles were removed from the uterine lumen by manual extirpation and separated from cotyledons. Endometrial tissue (0.5g) was collected by using Kenny's biopsy apparatus. For all samples, concentrations of potentially active Ceftiofur derivatives were quantified using an HPLC assay. Within 2h (serum), 4h (endometrium), and 12h (caruncles, cotyledons, lochia) after C1 and during the entire study period, mean concentration of Ceftiofur derivatives exceeded the reported minimum drug concentrations required to inhibit the growth of 90% of isolates for relevant bacteria such as Escherichia coli, Fusobacterium necrophorum, and Arcanobacterium pyogenes. Only in single samples did concentrations decrease temporarily below the reported minimum drug concentrations required to inhibit the growth of 90% of isolates.
Aldert A. Bergwerff - One of the best experts on this subject based on the ideXlab platform.
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Determination of Ceftiofur derivatives in serum, endometrial tissue, and lochia in puerperal dairy cows after subcutaneous administration of Ceftiofur crystalline free acid
Journal of dairy science, 2011Co-Authors: T.s. Witte, Michael Iwersen, T Kaufmann, Peter Scherpenisse, Aldert A. Bergwerff, Wolfgang HeuwieserAbstract:Abstract Puerperal uterine infections are often associated with decreased reproductive performance in dairy cows. Routine treatment protocols include the systemic administration of antibiotics. Antibiotic drugs, however, should be administered daily over at least 5 d. The objective of this study was to determine concentrations of Ceftiofur derivatives in serum, endometrial tissue, and lochia after subcutaneous administration of Ceftiofur crystalline free acid in 6 clinically healthy puerperal dairy cows with normal parturition. Samples were taken immediately before treatment, 2h after, and then every 24h over a 7-d period. Concentrations of Ceftiofur derivatives were quantified using an HPLC assay. In serum and endometrial tissue, Ceftiofur derivatives could be detected above the reported minimum drug concentrations required to inhibit relevant pathogens such as Escherichia coli and Arcanobacterium pyogenes over a 7-d period. Concentrations of desfuroylCeftiofuracetamide at 5 d after administration of Ceftiofur crystalline free acid were 1.21±0.61 μg/mL in serum, 0.86±0.61 μg/mg in endometrial tissue, and 0.96±1.15 μg/mL in lochia. In lochia, mean concentrations of Ceftiofur derivatives also remained above the minimal inhibitory concentration of relevant pathogens, but showed greater variations between cows.
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Ceftiofur derivatives in serum uterine tissues cotyledons and lochia after fetal membrane retention
Journal of Dairy Science, 2006Co-Authors: M Drillich, Peter Scherpenisse, Aldert A. Bergwerff, S Arlt, S Kersting, W HeuwieserAbstract:Abstract The objective of the study was to determine concentrations of Ceftiofur derivatives after subcutaneous application of Ceftiofur hydrochloride in cows with retained fetal membranes. Concentrations of Ceftiofur derivatives detected as desfuroylCeftiofuracetamide were determined in blood serum, endometrium, caruncles, cotyledons, and lochia during 72h. After induction of parturition, 2 primiparous and 4 multiparous cows having retained fetal membranes for at least 12h were studied. All cows received 3 consecutive injections (C1 to C3; 24h apart) of 1-mg Ceftiofur equivalents per kilogram of body weight as Ceftiofur hydrochloride sterile suspension. Samples of blood, endometrium, caruncles, cotyledons, and lochia were collected immediately before each injection (0h) and again at 4, 12, and 24h after C1, C2, and C3. Blood samples were collected from coccygeal vessels. Caruncles were removed from the uterine lumen by manual extirpation and separated from cotyledons. Endometrial tissue (0.5g) was collected by using Kenny's biopsy apparatus. For all samples, concentrations of potentially active Ceftiofur derivatives were quantified using an HPLC assay. Within 2h (serum), 4h (endometrium), and 12h (caruncles, cotyledons, lochia) after C1 and during the entire study period, mean concentration of Ceftiofur derivatives exceeded the reported minimum drug concentrations required to inhibit the growth of 90% of isolates for relevant bacteria such as Escherichia coli, Fusobacterium necrophorum, and Arcanobacterium pyogenes. Only in single samples did concentrations decrease temporarily below the reported minimum drug concentrations required to inhibit the growth of 90% of isolates.