The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
David Smith - One of the best experts on this subject based on the ideXlab platform.
-
influence of angiotensin ii induced alterations in renal flow on excretion of Cefonicid in isolated perfused rat kidneys
Antimicrobial Agents and Chemotherapy, 1992Co-Authors: C A Rodriguez, David SmithAbstract:Abstract The effects of variations in renal perfusate flow on the excretion of Cefonicid was examined in isolated perfused rat kidneys. Cefonicid, an expanded-spectrum cephalosporin, is primarily eliminated by active tubular secretion and is neither metabolized nor reabsorbed in the isolated kidney. We used angiotensin II (AII), a strong vasoconstrictor hormone of the afferent and the efferent arterioles in the kidney, to determine whether the renal and secretion clearances, as well as the excretion ratio (ER = CLR/[fu x GFR], where CLR is renal clearance, fu is the unbound fraction, and GFR is glomerular filtration rate), of this low-extraction compound can be altered by a decreased perfusion flow. Control studies were performed in the absence (n = 5) and presence (n = 4) of AII; Cefonicid studies were performed in the absence (n = 4) and presence (n = 5) of AII. AII (1 to 4 ng/min) and Cefonicid (5 to 10 micrograms/min) were infused into the perfusate. Cefonicid was assayed by high-performance liquid chromatography, and its protein binding was determined by ultrafiltration. AII decreased the perfusate flow rate and increased the renal vascular resistance and filtration fraction of the isolated kidney in the presence and absence of Cefonicid. The glomerular filtration rate remained unchanged among the groups. The fractional excretion of glucose was low and steady, indicating a well-preserved tubular function. Although the unbound fraction was unchanged between treatments, the renal and secretion clearances and the excretion ratio of Cefonicid were reduced by about 40% in the presence of AII (excretion ratios, 10.3 without AII versus 6.03 with AII). These results suggest that the altered clearance parameters of Cefonicid are the result of a flow-induced change in the intrinsic secretory transport of the drug.
-
influence of the unbound concentration of Cefonicid on its renal elimination in isolated perfused rat kidneys
Antimicrobial Agents and Chemotherapy, 1991Co-Authors: C A Rodriguez, David SmithAbstract:The effect of variations in plasma protein binding on the renal excretion of Cefonicid was assessed by using isolated perfused rat kidneys. Cefonicid exhibits preferential binding ex vivo to human serum albumin (HSA), as opposed to bovine serum albumin (BSA), and is eliminated mainly by tubular secretion, a process that was reported to be dependent on the total drug concentration. This contradicts previous studies with antimicrobial compounds and other drugs of low renal extraction in which the unbound drug concentration was shown to be the driving force for carrier-mediated tubular transport. To clarify this discrepancy, we performed perfusion studies by using 6% BSA at initial concentrations of 200 micrograms/ml (n = 6) and 20 micrograms/ml (n = 9) and in a combination of 4% BSA plus 2% HSA at initial concentrations of 200 micrograms/ml (n = 4). The excretion ratio [ER = CLR/(fu x GFR)] of Cefonicid decreased with increasing unbound concentrations, whereas no apparent relationship with the total concentration was evident. At similar total concentrations of Cefonicid, the renal clearance remained unchanged; the secretion clearance increased significantly in the 4% BSA-2% HSA experiments, reflecting the reduced unbound fraction and unbound drug concentration of Cefonicid. The excretion ratio data were compatible with a model in which Michaelis-Menten kinetics were required to describe active transport and secretion was dependent on the unbound Cefonicid concentration. As a result, changes in plasma protein binding as a result of drug interactions or disease states could significantly influence the tubular transport capability of compounds with low renal extraction.
C A Rodriguez - One of the best experts on this subject based on the ideXlab platform.
-
influence of angiotensin ii induced alterations in renal flow on excretion of Cefonicid in isolated perfused rat kidneys
Antimicrobial Agents and Chemotherapy, 1992Co-Authors: C A Rodriguez, David SmithAbstract:Abstract The effects of variations in renal perfusate flow on the excretion of Cefonicid was examined in isolated perfused rat kidneys. Cefonicid, an expanded-spectrum cephalosporin, is primarily eliminated by active tubular secretion and is neither metabolized nor reabsorbed in the isolated kidney. We used angiotensin II (AII), a strong vasoconstrictor hormone of the afferent and the efferent arterioles in the kidney, to determine whether the renal and secretion clearances, as well as the excretion ratio (ER = CLR/[fu x GFR], where CLR is renal clearance, fu is the unbound fraction, and GFR is glomerular filtration rate), of this low-extraction compound can be altered by a decreased perfusion flow. Control studies were performed in the absence (n = 5) and presence (n = 4) of AII; Cefonicid studies were performed in the absence (n = 4) and presence (n = 5) of AII. AII (1 to 4 ng/min) and Cefonicid (5 to 10 micrograms/min) were infused into the perfusate. Cefonicid was assayed by high-performance liquid chromatography, and its protein binding was determined by ultrafiltration. AII decreased the perfusate flow rate and increased the renal vascular resistance and filtration fraction of the isolated kidney in the presence and absence of Cefonicid. The glomerular filtration rate remained unchanged among the groups. The fractional excretion of glucose was low and steady, indicating a well-preserved tubular function. Although the unbound fraction was unchanged between treatments, the renal and secretion clearances and the excretion ratio of Cefonicid were reduced by about 40% in the presence of AII (excretion ratios, 10.3 without AII versus 6.03 with AII). These results suggest that the altered clearance parameters of Cefonicid are the result of a flow-induced change in the intrinsic secretory transport of the drug.
-
influence of the unbound concentration of Cefonicid on its renal elimination in isolated perfused rat kidneys
Antimicrobial Agents and Chemotherapy, 1991Co-Authors: C A Rodriguez, David SmithAbstract:The effect of variations in plasma protein binding on the renal excretion of Cefonicid was assessed by using isolated perfused rat kidneys. Cefonicid exhibits preferential binding ex vivo to human serum albumin (HSA), as opposed to bovine serum albumin (BSA), and is eliminated mainly by tubular secretion, a process that was reported to be dependent on the total drug concentration. This contradicts previous studies with antimicrobial compounds and other drugs of low renal extraction in which the unbound drug concentration was shown to be the driving force for carrier-mediated tubular transport. To clarify this discrepancy, we performed perfusion studies by using 6% BSA at initial concentrations of 200 micrograms/ml (n = 6) and 20 micrograms/ml (n = 9) and in a combination of 4% BSA plus 2% HSA at initial concentrations of 200 micrograms/ml (n = 4). The excretion ratio [ER = CLR/(fu x GFR)] of Cefonicid decreased with increasing unbound concentrations, whereas no apparent relationship with the total concentration was evident. At similar total concentrations of Cefonicid, the renal clearance remained unchanged; the secretion clearance increased significantly in the 4% BSA-2% HSA experiments, reflecting the reduced unbound fraction and unbound drug concentration of Cefonicid. The excretion ratio data were compatible with a model in which Michaelis-Menten kinetics were required to describe active transport and secretion was dependent on the unbound Cefonicid concentration. As a result, changes in plasma protein binding as a result of drug interactions or disease states could significantly influence the tubular transport capability of compounds with low renal extraction.
Y Shoenfeld - One of the best experts on this subject based on the ideXlab platform.
-
comparative clinical study of Cefonicid chloramphenicol and penicillin in community acquired pneumonia
International Journal of Molecular Medicine, 1998Co-Authors: Yaniv Sherer, Erez Bakshi, P Rotman, Y Levy, Y ShoenfeldAbstract:Community-acquired pneumonia is one of the most common infectious conditions that require hospitalization. When intravenous treatment is indicated, Cefonicid is usually the drug of choice. The aim of this study was to find out if chloramphenicol, which is superior to the standard drugs from a financial point of view, could serve as an equally efficient treatment, especially in the elderly. The outcomes of 3 pneumonia patient groups who were either treated with Cefonicid, chloramphenicol or penicillin-G (n = 59, 17, 24, respectively) were retrospectively compared. Data about demographic characteristics of the patients, clinical outcomes, rehospitalization rates, duration of improvement/treatment/ hospitalization and clinical laboratory tests were obtained from each patient's medical records. Only minor differences (even though occasionally significant) were found with respect to rehospitalization and improvement rates, duration of hospitalization, treatment and improvement, death rates and clinical laboratory tests. However, chloramphenicol patients were found to be significantly older than Cefonicid patients. Moreover, no bone-marrow suppression was associated with chloramphenicol treatment. All 3 drugs tested seem to have the same efficacy. We conclude that since chloramphenicol is as safe as, and much cheaper than Cefonicid, this antibiotic agent is not inferior to the others, its usage in older patients with pneumonia should be considered.
R L Wagner - One of the best experts on this subject based on the ideXlab platform.
-
Cefonicid versus clindamycin prophylaxis for head and neck surgery in a randomized double blind trial with pharmacokinetic implications
Antimicrobial Agents and Chemotherapy, 1991Co-Authors: D Swanson, R A Maxwell, J T Johnson, R L WagnerAbstract:Perioperative single-dose antibiotic prophylaxis of Cefonicid was compared with clindamycin in a prospective, randomized, double-blind trial of patients undergoing oncologic head and neck surgery. Antibiotics were administered intravenously beginning 1 to 2 h preoperatively. Cefonicid, 1 g, was given as a single dose. Clindamycin, 600 mg, was administered every 8 h for a total of four doses. Blood and wound drainage samples were collected for 24 h following the dose of Cefonicid and assayed for total and free Cefonicid concentrations, using reverse-phase high-performance liquid chromatography. Although total concentrations of Cefonicid in both serum and wound drainage exceeded the MIC for 90% of the isolates of common bacterial pathogens for 24 h, free concentrations in serum and wound drainage (11.0 and 14.9% of total concentrations) were subinhibitory within 6 h following administration. Free concentrations of Cefonicid in the postoperative wound drainage were subinhibitory for the entire study period, both perioperatively and postoperatively. Postoperative wound infection occurred significantly (P less than 0.05) more frequently in patients receiving Cefonicid (24%) as compared with those receiving clindamycin (8.2%). The relatively low free levels of Cefonicid achieved in serum and wound drainage were attributed to the high degree of protein binding (89% in serum) and may be related to the poor clinical outcome.
Sydney M. Finegold - One of the best experts on this subject based on the ideXlab platform.
-
Effect of beta-lactamase inhibitors on the activities of various beta-lactam agents against anaerobic bacteria.
Antimicrobial agents and chemotherapy, 1991Co-Authors: Hannah M. Wexler, E Molitoris, Sydney M. FinegoldAbstract:The in vitro activities of several new beta-lactam-beta-lactamase inhibitor combinations (piperacillin plus tazobactam, ceftizoxime and Cefonicid with sulbactam and clavulanic acid, and ampicillin plus 8 micrograms of sulbactam per ml) were tested with anaerobic bacteria and compared with known beta-lactam-beta-lactamase inhibitor combinations and other potent antianaerobe agents. All the combinations tested (except for the Cefonicid-inhibitor combinations) were active against almost all strains of the Bacteroides fragilis group. This report indicates that beta-lactamase inhibitors may improve the activity of beta-lactam agents with marginal activity against the B. fragilis group.