Pharmacokinetics of ceftazidime in patients with renal insufficiency

Welage, Lynda S.; Schultz, Rebecca; Schentag, J J

doi:10.1128/aac.25.2.201

Cited by 55 publications

(43 citation statements)

References 9 publications

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“…The volume of distribution of the drug was unaffected by the state of renal impairment, and therefore drug clearance was directly proportional to GFR. Similar results have been reported by Ackerman et al (1984), Fillastre et al (1983), Homer et al (1984a, Leroy et al (1984) and by Welage et al (1984).…”

Section: Cejtazidimesupporting

confidence: 93%

Clinical Pharmacokinetics of the Third Generation Cephalosporins

Balant

Dayer

Auckenthaler

1985

Clinical Pharmacokinetics

106

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At the present time, the third generation cephalosporins that are already on the market or close to this point include cefsulodin, cefotaxime, cefoperazone, latamoxef, ceftriaxone, ceftazidime, ceftizoxime and cefotetan. Other newer compounds are also under development but have not been included in this review. None of the third generation compounds is suitable for oral administration and, accordingly, their pharmacokinetics have been studied only after intravenous and intramuscular administration. Microbiological assays and HPLC methods have been used for the measurement of plasma/serum, urine, bile and cerebrospinal fluid (CSF) concentrations. As found with cefotaxime, microbiological assays should only be used when the full metabolite spectrum of a particular drug is known, as otherwise, the presence of microbiologically active metabolites may lead to erroneous conclusions. Under normal conditions, the major route of elimination is via the kidneys for cefsulodin, latamoxef, ceftazidime, ceftizoxime and cefotetan. In contrast, cefoperazone is mainly eliminated in the bile, whereas cefotaxime and ceftriaxone depend both on the liver and the kidneys for their elimination. With the exception of ceftriaxone, which has a longer elimination half-life (i.e. around 8 hours), all the other third generation cephalosporins have a t1/2 ranging between 1.5 and 2.5 hours. Plasma protein binding is variable from one compound to another. However, the clinical relevance of this parameter is not clearly established since tissue penetration also depends on the relative affinity of the drug for tissue components. Third generation cephalosporins seem to penetrate adequately into the CSF and, thus pharmacokinetically appear to be appropriate agents for the treatment of meningitis. The degree of modification of pharmacokinetic parameters by renal insufficiency or hepatic diseases depends, as for other drugs, on the extent to which the compound is excreted via the kidneys or the liver. The third generation cephalosporins have been extensively studied under these conditions and recommendations for dosage modification in special circumstances are available for most of them. The pharmacokinetics of some third generation cephalosporins may be modified in neonates and elderly patients. Accordingly, their use at the extremes of age must be accompanied by a closer than usual clinical monitoring of the patient. From a clinical point of view, the third generation cephalosporins possess reliable pharmacokinetic properties.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Cejtazidimesupporting

confidence: 93%

Clinical Pharmacokinetics of the Third Generation Cephalosporins

Balant

Dayer

Auckenthaler

1985

Clinical Pharmacokinetics

106

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“…There was a marked reduction in Cltot, reflecting slow elimination of the drug due to the poor renal function of our patients, The clearance rate was much lower than in the patients studied by Ljungberg and Nilsson-Ehle (11,12) and Naber et al (10), the decrease being related to the degree of renal impairment, as also noted in a study by H6ffler et al (7). The slow decline in the serum drug concentration resulted in large AUCs values, four times as large as those obtained in studies of younger subjects (3,7,8) but comparable with those obtained for both elderly patients (11,12) and younger patients with impaired renal function (19). The AUC correlated with renal capacity, as also found by Hfffier et al (7).…”

Section: Resultssupporting

confidence: 68%

“…The Vd of ceftazidime in steady state has been reported to average 0.21 l/kg in normal healthy individuals (4). In contrast to other investigators of patients in different age groups (4,7,(10)(11)(12)(13)19), we found a reduced Vd, possibly related not only to the low total body water content in elderly people (i.e. less water available to dissolve a water-soluble substance such as ceftazidime) but also to the dehydration often seen in the very old during acute infection.…”

Section: Resultsmentioning

confidence: 95%

Pharmacokinetics of ceftazidime in acutely Ill hospitalised elderly patients

Jönsson¹,

Walder

1992

Eur. J. Clin. Microbiol. Infect. Dis.

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The i.v. and i.m. dose pharmacokinetics of ceftazidime 1 g b.i.d. were investigated in steady state in 52 consecutive cases of hospitalised patients with underlying diseases and serious supervening bacterial infections. Following i.v. bolus injection, serum concentrations of greater than 4 mg/l persisted for 8 h in all patients. Compared to values found in younger patients studied previously, clearance was markedly reduced in the elderly, t1/2 beta more than doubled, the area under the curve four times enlarged and the apparent volume of distribution reduced. The values obtained in serum after i.m. injection were similar, though the peak concentration was delayed by about 2 h. The serum uptake was approximately 70%, and serum concentration was greater than 4 mg/l for 8 h. The concentrations in tissue fluid after i.v. administration were similar to those in serum, but the penetration into tissue fluid was slower and only 20% of that reported previously for young people. The elimination was slow, with greater than 4 mg/l maintained for 7 h. Tissue concentrations after i.m. injection were almost comparable with those after i.v. injection, but lagged behind by about 1 h. In conclusion, suitable concentrations in blood and tissue are attained with 1 g ceftazidime b.i.d., whether administered by the i.v. or i.m. route.

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“…Phase 1 studies have established the PK profile of avibactam in healthy volunteers and shown that avibactam is generally well tolerated and does not affect the PK or safety profile of ceftazidime . As avibactam is, like ceftazidime, predominantly excreted unchanged by the kidney, it is possible that impaired renal function affects avibactam clearance and, as a consequence, its plasma exposure . In the present phase 1 study, the primary objective was to characterize the PK of avibactam in adults with normal renal function and those with varying degrees of renal impairment who were administered a single 100‐mg avibactam dose by intravenous (IV) infusion over 30 minutes.…”

mentioning

confidence: 99%

Phase 1 Study Assessing the Pharmacokinetic Profile and Safety of Avibactam in Patients With Renal Impairment

Merdjan¹,

Tarral²,

Das

et al. 2016

The Journal of Clinical Pharmacology

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Avibactam is a non-β-lactam β-lactamase inhibitor intended for use as a fixed-dose combination with ceftazidime for the treatment of certain serious Gram-negative infections. As avibactam is primarily excreted unchanged in the urine, renal impairment may affect its pharmacokinetics. This phase 1 study investigated the effect of renal impairment and hemodialysis on avibactam pharmacokinetics and safety. Healthy controls and subjects with increasing degrees of renal impairment received a single 30-minute intravenous (IV) infusion of avibactam (100 mg). Anuric subjects requiring hemodialysis received the same infusion pre- and posthemodialysis, separated by a 7- to 14-day washout. Blood and urine samples were collected, and pharmacokinetics were analyzed using noncompartmental methods. The relationships between avibactam total plasma clearance (CL) or renal clearance (CL ) and creatinine clearance (CrCL) were evaluated by linear correlation analysis. Safety was also monitored. Increasing severity of renal impairment was associated with decreasing CL and CL and increasing exposure and terminal half-life (t ). Avibactam CL and CL demonstrated an approximately linear relationship with CrCL comparable to that previously observed for ceftazidime. In patients requiring hemodialysis, >50% of the administered avibactam was removed during a 4-hour hemodialysis session, demonstrating that avibactam should be administered after hemodialysis. No new safety findings were reported. To conclude, avibactam dose adjustment is warranted in patients with renal impairment based on the severity of impairment. Because the slope of the linear relationship between avibactam total plasma CL and CrCL is similar to that of ceftazidime, renal impairment dose adjustments should maintain the currently advised 4:1 ratio of ceftazidime:avibactam.

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Pharmacokinetics of ceftazidime in patients with renal insufficiency

Cited by 55 publications

References 9 publications

Clinical Pharmacokinetics of the Third Generation Cephalosporins

Clinical Pharmacokinetics of the Third Generation Cephalosporins

Pharmacokinetics of ceftazidime in acutely Ill hospitalised elderly patients

Phase 1 Study Assessing the Pharmacokinetic Profile and Safety of Avibactam in Patients With Renal Impairment

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