Excretion of Cephaloridine and Cephalothin in Patients with Renal Impairment

Kunin, Calvin M.; Atuk, Nuzhet O.

doi:10.1056/nejm196603242741205

Cited by 68 publications

(20 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The exponential rale of elimination of cephalexin from the blood stream enables T'/s-values to be extra polated from semilogaritbmic plots of serum levels on the descend ing branch of the curves [Kunin and Atuk, 1966], Half-life values in the 11 patients with normal renal function averaged 1.2 h ( fig. 2) (range 0.8-1.4 h) (table II).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Human Pharmacokinetics of Cephalexin

Bergan

Midtvedt

Erikssen³

1970

Pharmacology

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

“…This is due to the relatively low average T1 /« of 1.2 h in patients with normal renal function. The T'/a of cephalothin and cephaloridine are 0.85 and 1.52, respectively [Kunin and Atuk, 1966].…”

Section: Discussionmentioning

confidence: 99%

Human Pharmacokinetics of Cephalexin

Bergan

Midtvedt

Erikssen³

1970

Pharmacology

View full text Add to dashboard Cite

“…Cephapirin, like cephalothin and cephaloridine (7,9), is removed from the blood by hemodialysis. Extrapolation of the free antibiotic concentration curve in blood after dialysis (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…From the six patients who underwent dialysis, venous blood, arterial blood, and dialysate were obtained 0. 5,1,2,3,4,6,7,8,9, and 48 hr after cephapirin was injected. Venous blood and urine were obtained from the 10 nondialyzed patients 0.5, 1, 2, 4, and 6 hr after the injection of 1.0 g of cephapirin sodium.…”

mentioning

confidence: 99%

Effect of Hemodialysis and Renal Failure on Serum and Urine Concentrations of Cephapirin Sodium

McCloskey

Terry

McCracken

et al. 1972

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Six patients undergoing chronic hemodialysis and 10 patients with chronic renal insufficiency hospitalized for nondialytic therapy received 1.0 g of cephapirin sodium by the intravenous route. Cephapirin, 7-(pyrid-4-yl thioacetamido) cephalosporonate, is a new semisynthetic derivative of 7-aminocephalosporanic acid effective in vitro against gram-positive and gram-negative microorganisms. Concentrations of cephapirin necessary to inhibit Diplococcus pneumoniae, Mycobacterium tuberculosis (H37Rv), and Enterobacter sp. in vivo are less than those of cephalothin (3). The amount of cephapirin bound to human serum proteins is less than that of cephalothin similarly bound (3). Seventeen children responded "satisfactorily" to cephapirin treatment of pneumonia, lung abscess, and urinary-tract and soft-tissue infections (4).This report describes the clearance of cephapirin from the blood during hemodialysis and the urinary excretion of intravenously administered cephapirin during nondialytic treatment of azotemia.MATERIALS AND METHODS Patient population. Of the 16 azotemic patients who participated in the study, 10 were hospitalized for nondialytic therapy of chronic renal failure and 6 were undergoing extracorporal hemodialysis two times weekly in anticipation of renal transplantation. The mean serum creatinine of the dialyzed patients was 13.1 mg/100 ml; that of the nondialyzed patients was 90 6.6 mg/100 ml. Hemodialysis lasted 6 hr and was performed by use of a twin-coil Travenol RSP dialyzer with a Visking UF 145 membrane. Each patient received 1.0 g of cephapirin sodium intravenously over a period of 5 min. From the six patients who underwent dialysis, venous blood, arterial blood, and dialysate were obtained 0. 5,1,2,3,4,6,7,8,9, and 48 hr after cephapirin was injected. Venous blood and urine were obtained from the 10 nondialyzed patients 0.5, 1, 2, 4, and 6 hr after the injection of 1.0 g of cephapirin sodium.Cephapirin concentration. Serum or plasma was diluted with an equal volume of acetone-buffer (50% acetone-50% pH 6.0 phosphate buffer, v/v) and centrifuged at 2,000 rev/min for 10 min to remove precipitated protein. Urine samples were diluted with pH 6.0 phosphate buffer. Serum and urine were assayed immediately by the agar plate bioassay method (5). Sarcina lutea (ATCC 9341) was incubated at 32 C for 18 hr, and was diluted so that a 10% suspension produced 20%O light transmission at 580 nm. This suspension was the inoculum for all assays. The diameter of the inhibition zone surrounding each unknown sample was measured, and the cephapirin concentration was determined by comparison with a standard curve relating reference cephapirin concentrations (0.1 to 0.5 ,ug/ml) to zone of inhibition produced by the reference concentration. Reference concentrations of cephapirin were included with each assay of experimental serum, plasma, or urine.

show abstract

“…Infections remain among the most common causes of hospitalization and death (6). Contributing to a lengthy hospitalization may be the administration of parenteral drugs by recommended schedules (3)(4)(5). If infections can be treated by administering antibiotics only at the time of HD, the benefits will include cost reduction, the length of hospital stay, and the achievement of a full course of therapy.…”

mentioning

confidence: 99%

Hemodialysis-Associated Infections: Treatment with Cephapirin

Berman¹,

Boughton

Sugihara

et al. 1978

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Large doses of cephapirin (50 mg/kg) administered during the first and last half hours of routine hemodialysis produced effective antimicrobial serum concentrations for 48 h. Repetitive administration during five successive hemodialysis sessions did not result in accumulation or accelerated metabolism of cephapirin. Ten infectious episodes in nine patients were treated in this manner with good clinical results and no toxicity.Much of the morbidity of chronic renal failure has not been relieved by hemodialysis (HD). Infections remain among the most common causes of hospitalization and death (6). Contributing to a lengthy hospitalization may be the administration of parenteral drugs by recommended schedules (3)(4)(5). If infections can be treated by administering antibiotics only at the time of HD, the benefits will include cost reduction, the length of hospital stay, and the achievement of a full course of therapy.Cephapirin, a semisynthetic cephalosporin for parenteral use, has been chosen to test this proposal. It is a derivative of 7-aminocephalosporanic acid and is metabolized to desacetylcephapirin, which also appears to be microbiologically active (7). The half-life of 1.0 g of cephapirin during HD is 107 min (5). There are no data regarding the dose of cephapirin that must be administered during HD to maintain sufficient antibacterial activity for the interdialysis period, usually a minimum of 42 h. We have performed single-and multiple-dose pharmacokinetic studies to establish dosage schedules and treated 10 infectious episodes to determine the feasibility of this approach. MATERIALS AND METHODSSingle-dose pharmacokinetics. Nine patients with end-stage renal disease and no other active clinical illness whose creatinine clearances were <5 ml/min were studied on either a Travenol, Lifemed, or Milton Roy recirculating single-pass HD machine using extracorporeal EX-23 coils. A 40-mg/kg amount of cephapirin was administered by intravenous infusion over 30 min, starting 1 h before HD; arterial and venous samples were drawn at the initiation of HD, at 1, 2, and 4 h, and at the completion of HD. Multiple-dose pharmacokinetics. Five patients received 50 mg of cephapirin per kg in 75 ml of normal saline during the first 30 min of a routine HD (predialysis dose) and then received a duplicate amount of the drug during the last 30 min of HD (postdialysis dose). Cephapirin was administered through the arterial line of the dialyzer and was drawn in by the negative pressure of the machine. Venous blood samples were obtained at the conclusion of each HD period (peak) and just before the initiation of the next session (trough). HD was conducted for 5.5 h on a schedule of three times a week; the patients were studied for five consecutive HD periods. After administration of the last dose of cephapirin, serum concentrations were assayed at 24, 48, and 72 h.Plasma assay cephapirin. Arterial and venous blood samples were drawn in 5-ml sodium heparin vacuum tubes. Blood samples were placed immediately in an ice bath, and the pla...

show abstract

Excretion of Cephaloridine and Cephalothin in Patients with Renal Impairment

Cited by 68 publications

References 9 publications

Human Pharmacokinetics of Cephalexin

Human Pharmacokinetics of Cephalexin

Effect of Hemodialysis and Renal Failure on Serum and Urine Concentrations of Cephapirin Sodium

Hemodialysis-Associated Infections: Treatment with Cephapirin

Contact Info

Product

Resources

About