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

Abstract

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.

Pharmacokinetics of Cefamandole in Patients with Renal Failure

“…The serum tl2 of cefamandole in patients with stable renal impairment and serum creatinine values .5 mg/100 ml was approximately 10 to 15 times greater than that obtained in volunteers with normal renal function. The tl,2 was greater in patients with higher serum cre- atinine values as has been observed with other cephalosporin derivatives (1,8). The mean AVD of 21.92 liters in the group of 10 patients with renal failure was higher than that of 17.11 liters found in healthy volunteers.…”

Treatment of Pneumonia and Other Serious Bacterial Infections with Cephapirin

“…Two patients with abnormal renal function, one of whom was anuric and on a hemodialysis program, had considerably elevated serum levels without recognized toxicity. Hemodialysis was effective in partially removing cephapirin from the blood, as documented by McCloskey et al (12).…”

Pharmacokinetics of new broad-spectrum cephamycin, YM09330, parenterally administered to various experimental animals

“…Cephalosporins, such as cephalothin (3,7,19), cephapirin (2,9), cephacetrile (8,12), cefotaxine (4,20), with an acetoxymethyl substituent at the 3-position of,-lactam skeleton are metabolized to less active metabolites. YM09330 differs from the above cephalosporins with respect to a substituent at the 3-position.…”