Elimination kinetics of ceftizoxime in humans with and without renal insufficiency

Abstract

The pharmacokinetics of a single 500-mg intramuscular dose of ceftizoxime were studied in 11 healthy adult volunteers and in 22 patients with various degrees of renal dysfunction. The mean serum half-life of ceftizoxime was 1.44 h in normal subjects and 30.2 h in hemodialysis patients. A significant correlation (P less than 0.001) between the elimination rate constant of ceftizoxime and creatinine clearance was demonstrated. The mean urinary recovery in normal subjects was 75.6% within 6 h of dosage; recovery decreased progressively with reduced renal function.

Identification and Quantitative Assessment of Uremic Solutes as Inhibitors of Renal Organic Anion Transporters, OAT1 and OAT3

“…Although famotidine is also a substrate of OCT2 in vitro , addition of an OCT2 inhibitor, cimetidine, produced little effect on its renal clearance suggesting that OCT2 plays little or no role in its transport in vivo . In the end, we analyzed 18 drugs from 13 published papers − and five NDAs. − Our analysis showed that for many drugs, CL sec normalized to GFR was reduced in patients with CKD Stage 4 (GFR = 15–29 mL/min) compared with patients with normal renal function (Figure b, p < 0.001). The disproportionate deterioration of CL sec in CKD was modeled using eq , which introduces a factor F x causing decreased CL sec in addition to decreased filtration as demonstrated by the ratio of CL sec to GFR between subjects with CKD and subjects with normal renal function.…”

Pharmacokinetics of Ceftazidime in Patients with Renal Insufficiency and in Those Undergoing Hemodialysis

“…The t u2P of ceftazi dime was prolonged as renal function de creased, being 9 times as long in group 5 as in group 1. This prolongation of the U/2P for ceftazidime was smaller than those for cefazolin [4], cefoxitin [6], cefmetazole [14] and ceftizoxime [13]. The results suggest that ceftazidime is eliminated partly by a route other than renal, for example by bili ary excretion [3], because no metabolites were detected in the serum by high-pres sure liquid chromatography or in the urine by bioautography [1], The total body clear ance and renal clearance decreased in par allel with the renal impairment, whereas the nonrenal clearance (total body clear ance-renal clearance; 9.7-17.5 ml/min) was not influenced by the severity of renal impairment.…”

Metabolism, Excretion, and Pharmacokinetics of [14C]‐Cefiderocol (S‐649266), a Siderophore Cephalosporin, in Healthy Subjects Following Intravenous Administration

“…It is known that ceftizoxime, which is an aminothiazolyl oximino cephalosporin without C-3 side chain moiety, is mainly excreted in the urine as unchanged drug at an excretion rate of approximately 80% of dose in the 6-hour urine after dosing. 21 It is known that N-methyl pyrrolidine moiety, which is a C-3 side chain of cefepime, is cleaved and detected in human and rat urine. 18,22 It is a common practice to radiolabel the compound at a chemically and metabolically stable position; however, the radiolabeled position of cefiderocol was in catechol moiety at the C-3 side chain because the disposition of an aminothiazolyl oximino cephalosporin such as ceftizoxime is well characterized and the catechol moiety was a unique structure for cefiderocol in the aminothiazolyl oximino cephalosporins.…”

“…The structure of cefiderocol is similar to the other marketed aminothiazolyl oximino cephalosporins such as ceftizoxime, cefotaxime, cefepime, and ceftazidime except for the C‐3 side chain with pyrrolidine linked to catechol moiety. It is known that ceftizoxime, which is an aminothiazolyl oximino cephalosporin without C‐3 side chain moiety, is mainly excreted in the urine as unchanged drug at an excretion rate of approximately 80% of dose in the 6‐hour urine after dosing . It is known that N ‐methyl pyrrolidine moiety, which is a C‐3 side chain of cefepime, is cleaved and detected in human and rat urine .…”