Comparison of cephaloridine renal accumulation and urinary excretion between normoglycemic and diabetic animals.

The renal toxicity of cephaloridine is reduced in a streptozotocin diabetic rat model. This study tested the hypothesis that renal cortical cephaloridine accumulation was diminished in diabetic rats. The following studies also investigated whether renal excretion was enhanced in diabetic rats. Male Fischer 344 rats were randomly divided into normoglycemic or diabetic groups. Diabetes was induced by injection (intraperitoneal, i.p.) of 35 mg/kg streptozotocin. Normoglycemic and diabetic rats were injected (i.p.) with 1500 mg/kg cephaloridine. Peak plasma cephaloridine levels were similar in both groups. Renal cortical accumulation was diminished (P < 0.05) in the diabetic group 1 and 4 h after cephaloridine injection. Urinary cephaloridine excretion was enhanced (P < 0.05) in the diabetic group relative to the normoglycemic animals during the first 4 h after cephaloridine injection. Comparisons between normoglycemic and diabetic groups indicated renal cortical cephaloridine accumulation was lower in the diabetic group. These findings would support the hypothesis that reduced cephaloridine toxicity in diabetic animals was due to reduced renal cortical accumulation of the toxin. These data also demonstrate that cephaloridine excretion was enhanced in the diabetic group and may contribute to the diminished renal accumulation.

Effects of L-carnitine on the renal tubular transport of cephaloridine.

It has been demonstrated recently that cephaloridine (Cld) inhibits the tubular reabsorption of filtered carnitine (Carn) in the rabbit kidney. This interaction has suggested that the limited net cell-to-luminal fluid movement of Cld following its secretory transport across the antiluminal membrane might result from a balance of active Cld reabsorption by a Carn carrier at the brush border approximately equal to its secretion into the tubular fluid, rather than the previously proposed luminal membrane block. Studies were done to determine the effects of L-Carn, 750 mg/kg, i.v. on the tubular secretion and cortical concentrations of Cld, infused i.v. at a dose of 28 mg/kg (Carn:Cld molar ratio = 70:1). The fractional excretions of Cld during three consecutive periods of 10 min each, one before and two following the bolus infusion of Carn, were (means +/- SEM): 1.18 +/- 0.14, 1.20 +/- 0.14, and 1.16 +/- 0.11, respectively (N = 6 each; differences NS). Cortex-to-serum concentration ratios of Cld in control and Carn-treated rabbits were 10.43 +/- 0.32 and 10.16 +/- 0.86, respectively (NS). The data provide evidence against the reabsorptive transport of Cld by a Carn carrier, and do not support a model of balanced secretion and reabsorption as the cause of limited clearance despite significant secretory transport of Cld into the tubular cell.

1H-NMR spectroscopy as a means of monitoring nephrotoxicity as exemplified by studies with cephaloridine.

1. Male albino rats were dosed intravenously with either 0.9% saline or cephaloridine in saline at doses of 650, 750 or 950 mg kg-1 d-1 for 7 d. 2. Urine analysis on day 3, after two doses of cephaloridine showed dose-related increases in glucose, total protein, N-acetyl beta-D-glucosaminidase, gamma-glutamyltranspeptidase, alkaline phosphatase and lactate dehydrogenase. 1H-NMR spectroscopy showed corresponding disturbed profiles of products of intermediary metabolism indicative of a disruption of renal function. 3. By day 6, after five doses of cephaloridine, analysis by both 1H-NMR and conventional methods showed that all indices had returned to normal. 1H-NMR was demonstrated to provide useful complementary information to conventional techniques on the time course of the onset of the nephrotoxicity and the recovery phase, and was at least as sensitive as conventional urine analysis.

Separation of cephaloridine from the rat urine contaminated by feces and diet pellets in high-performance liquid chromatography. Pretreatment with strongly basic anion exchange resin following deproteinization.

In this study, a high-performance liquid chromatographic method including a treatment with ion exchange resin following a deproteinization treatment, was studied for determination of cephaloridine in the rat urine which was contaminated by pieces of feces and diet pellets. The solvent system used was 10% acetonitrile (v/v) in 0.1 M K2 HPO4-H3 PO4 buffer, pH 7.5, and this was isocratically eluted on a reversed-phase column of NOVA-PAK C18. The urine sample containing cephaloridine was deproteinized, treated with a strongly basic anion exchange resin of Dowex-1-Chloride, and then chromatographed. In comparison to the sample treated by the simple deproteinization, the residual substances after the deproteinization, which interfered the cephaloridine peak, were removed by the following treatment with Dowex-1-Chloride, as was confirmed using a three-dimensional computing spectrophotometric monitor. Thus, the present method is considered to be useful in determination of cephaloridine in such body fluids as urine in which many interfering substances are contained.

Comparison of the renal excretory mechanisms of cefmenoxime and other cephalosporins: effect of para-aminohippurate on renal clearance and intrarenal distribution of cephalosporins in rabbits.

The renal excretory mechanism of cefmenoxime in rabbits was compared with that of 6 other cephalosporins (cefotaxime, deacetylcefotaxime, cefotiam, cefazolin, cephaloridine, and cefsulodin). The clearance ratios (Cf-Drug/CInulin=CRf) of cefmenoxime (337) and cefazolin (73) were considerably higher than those of the 5 other cephalosporins (0.9-20). When p-amino-hippurate (PAH) was administered concurrently with each of the cephalosporins, the CRf values of the cephalosporins except for cefsulodin were significantly decreased. These findings indicate that cefmenoxime and the 5 other cephalosporins except cefsulodin are actively incorporated in the proximal tubular cells and secreted into the tubular lumen. In the case of cefotiam and cefsulodin, glomerular filtration tended to exceed urinary excretion with highest dose of PAH (40 mg/kg/minute), suggesting the possibility of tubular reabsorption of these drugs. On the other hand, glomerular filtration of cefmenoxime and the 4 other cephalosporins did not exceed urinary excretion. The drug concentration ratio of the cortex to medulla indicated that the tubular cell level of cefmenoxime was lower than, higher than, and similar to those of cephaloridine, cefotaxime, and the remaining cephalosporins, respectively. These results demonstrate that the renal excretory mechanisms of cefmenoxime is similar to that of cefazolin but not to that of the remaining cephalosporins.

[Use of Ceporin after a cadaveric kidney allograft]. / Primenenie tseporina u bol'nykh posle allotransplantatsii trupnoi pochki.

Cephaloridin (ceporin of "Pliva", Yugoslavia) was used in the treatment of patients after allotransplantation of the kidney from a cadaver during the early postoperative period with a purpose of prevention (5 patients) and therapy of complications, such as pneumonia (7 patients), sepsis (3 patients), pyelonephritis of the transplanted kidney (4 patients). The drug levels in the blood serum and urine were determined 1, 2, 4, 6, 8 and 24 hours after the administration. The drug was used with regard for the transplant function estimated by the data of the glomerular filtration and concentration of the nitrous residues in the blood. The antibiotic dose depended on the transplant function. The study provided some recommendations as for the ceporin use in therapy of such population of patients.

Renal excretion of cephapirin and cephaloridine: evidence for saturable tubular reabsorption.

Drug concentrations in plasma and urine were determined in 5 healthy subjects after intravenous infusion of 1 gm cephapirin and cephaloridine. Sampling of blood and urine was frequent and prolonged. Specimens were analyzed by high-pressure liquid chromatography (HPLC). Renal clearance of cephapirin decreased to less than 5% of control in all subjects when drug concentrations in plasma and urine declined. Cephaloridine clearance decreased to a lesser extent. Our findings suggest that, besides tubular secretion and glomerular filtration, a saturable and probably active tubular reabsorption is also involved in the renal handling of these two cephalosporins. The saturable reabsorption process was characterized by its Michaelis-Menten constant Km and its maximum transport capacity Tm.

Half-life of cephaloridine in dogs with reduced renal function.

Various degrees of renal insufficiency were produced in 9 dogs by nephrectomy, or segmental ligation of the branches of the renal artery, or both. The serum half-life of cephaloridine, measured after a single intramuscular injection, increased progressively as renal function decreased. In dogs with 85% reduction in renal mass, serum half-life was approximately 3 times that of control dogs. To prevent accumulation of cephaloridine in dogs with renal dysfunction, a modified dose schedule was established on the basis of these experimental results.