Single-dose ceftriaxone kinetics in liver insufficiency

Stoeckel, Klaus; Tuerk, Herfried; Trueb, Vreny

doi:10.1038/clpt.1984.210

Cited by 38 publications

(28 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The maximum binding capacity (N3) was found to be 1 mol of drug per mol of albumin, and the association constant (K3) was 2.5 x 104 M-'. These values are in close agreement with those reported previously (3,4,17,18,22,27).…”

Section: Methodssupporting

confidence: 83%

Characteristics of ceftriaxone binding to immunoglobulin G and potential clinical significance

Sun

Chow

Maderazo

1991

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The interaction between immunoglobulin G (IgG) and ceftriaxone was studied. Using an ultrafiltration method, we performed dose ranging studies at a ceftriaxone concentration range of 1 to 720 ,ug/ml kidney, the latter almost exclusively by glomerular filtration (2,14,24). Its elimination half-life is about 8 h (2,25,26). The relatively long half-life is at least partly a direct consequence of its substantial protein binding and the absence of renal tubular secretion (2, 25). MATERIALS AND METHODSFree concentrations of ceftriaxone (Cf) were determined by ultrafiltration (23,30) by using the CETRIFREE micropartition system (Amicon Division, W. R. Grace & Co., Beverly, Mass.). Samples were equilibrated for 30 min at 37°C and were then centrifuged at 1,500 x g for 20 min. The free concentration was determined from the ultrafiltrate.The ceftriaxone concentrations in the ultrafiltrate and in phosphate-buffered saline (PBS) were determined by the spectrophotometric method (model 250; Gilford Instrument Laboratories Inc., Oberlin, Ohio). The maximum absorption wavelength of ceftriaxone in PBS, ultrafiltered PBS, ultrafiltered IgG in PBS solution, and ultrafiltered albumin in PBS solution was 240 nm. At a concentration of 1 jig/ml, the within-day coefficients of variation were 0.36% in PBS buffer solution and 2.91% in ultrafiltered IgG or ultrafiltered albumin solutions. The overall day-to-day coefficient of variation was 4.5%, which was obtained for slopes of standard curves over a 4-month period. The ceftriaxone concentration in plasma ultrafiltrate was determined at a wavelength of 275 nm. At this wavelength, a plasma ultrafiltrate blank has a very low absorption. Drug-free samples were used as blank controls for all drug concentration determinations.Preliminary experiments indicated that ceftriaxone does not bind to the filter membrane, regardless of whether PBS or plasma ultrafiltrate is used as the solvent medium. Consequently, PBS buffer was used as the solvent medium in subsequent experiments.Binding of ceftriaxone to IgG and/or albumin. The binding

show abstract

Section: Methodssupporting

confidence: 83%

Characteristics of ceftriaxone binding to immunoglobulin G and potential clinical significance

Sun

Chow

Maderazo

1991

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…However, the free fraction of antibiotic did increase because of the reduced protein binding. These results differ slightly from those observed in the studies with patient volunteers cited above (Jehl et al, 1990;Mazzei et al, 1993;Stoeckel et al, 1984). Unlike the single-dose ceftriaxone pharmacokinetic studies in uninfected cirrhotic patients, we measured peak serum concentrations at steady state on day 3 of therapy in rats with pneumococcal pneumonia.…”

Section: Discussioncontrasting

confidence: 52%

“…In a single-dose pharmacokinetic study, Stoeckel et al, (1984) found that when compared with normal controls, patients with chronic liver disease had significantly decreased mean nonrenal clearance of unbound ceftriaxone. The elimination half-life (t 1/2 b), however, was not influenced by chronic liver insufficiency (Stoeckel et al, 1984). Others (Hary et al, 1989) conducted a similar study in cirrhotic patients with ascites and also found no change in t 1/2 b.…”

Section: Discussionmentioning

confidence: 99%

Effect of cirrhosis on antibiotic efficacy in a rat model of pneumococcal pneumonia

Preheim¹,

Olsen²,

Yue³

et al. 2005

Diagnostic Microbiology and Infectious Disease

View full text Add to dashboard Cite

A rat model was used to study the effects of cirrhosis on antibiotic therapy of pneumococcal pneumonia. Cirrhotic and control male Sprague-Dawley rats were infected transtracheally with type 3 Streptococcus pneumoniae. Treatment began 18 h later with phosphatebuffered saline (PBS), azithromycin (50 mg/kg), trovafloxacin (50 mg/kg), or ceftriaxone (100 mg/kg) injected subcutaneously twice daily for 5 days. Antibiotic concentrations were measured by high-performance liquid chromatography. Azithromycin, trovafloxacin, and ceftriaxone were all equally effective at preventing mortality in both cirrhotic and normal rats. Free fraction area under the curve to minimum inhibitory concentration ratio (AUC/MIC) and maximum calculated serum concentration to MIC ratio (C max /MIC) and percent time that the serum concentration exceeded the MIC (%T N MIC) were greater for ceftriaxone compared with azithromycin or trovafloxacin. Azithromycin achieved higher concentrations in bronchoalveolar lavage fluid (BALF), epithelial lining fluid (ELF), and BAL white blood cells than ceftriaxone or trovafloxacin in cirrhotic rats. Macrolide, h-lactam, or fluoroquinolone antibiotic efficacy in a pneumococcal pneumonia model does not appear to be affected by hepatic cirrhosis. Published by Elsevier Inc.

show abstract

“…In fact, its ease of use and the quality of its tolerability, which have been shown in other patient categories, encourage us to use it on a regular basis when an infection caused by susceptible organisms occurs during the final 3 months of * Corresponding author. pregnancy (25,27,29). It has been shown that the systemic and local tolerabilities of CTX are excellent, with the absence of any nephrotoxicity (15,16).…”

mentioning

confidence: 99%

“…pregnancy (25,27,29). It has been shown that the systemic and local tolerabilities of CTX are excellent, with the absence of any nephrotoxicity (15, 16).…”

mentioning

confidence: 99%

Pharmacokinetics and protein binding of ceftriaxone during pregnancy

Bourget

Fernandez

Quinquis

et al. 1993

Antimicrob Agents Chemother

View full text Add to dashboard Cite

The purpose of the present work was to study the pharmacokinetics and the protein binding (free fraction of the drug) of ceftriaxone (CTX) during pregnancy. Nine pregnant women (ages, 20 to 34 years) whose gestational ages ranged from 28 4/7 to 40 5/7 weeks were included. The diagnosis of infection was established in all cases; i.e., four women had chorioamnionitis and five women had pyelonephritis. The following triple antibiotic therapy was infused with the aim of achieving cure: CTX, 2 g once every 24 h (constant rate over 60 min); tobramycin, 3 mg/kg of body weight once every 24 h; and ornidazole, 1 g/day. Two series of blood samples were collected, i.e., during the first day of treatment (on day 1), to establish the primary pharmacokinetic profile of CTX, and at the plateau (on day 7), to evaluate a possible accumulation of the drug.This was an open, noncompartmental study, with each patient serving as her own control. Concentrations of total and unbound CTX in serum were measured by a high-performance liquid chromatographic method. Pharmacokinetic analysis was done by a noncompartmental method. Data were compared by a Wilcoxon t test (a P value of .0.05 was considered significant). Data were also compared with those obtained for healthy subjects who received similar treatments. (i) The tolerance to treatment was excellent, and in all cases patients had a complete remission without premature delivery. (ii) No accumulation of CTX was noted during the treatment, and the profiles of the drug determined at days 1 and 7 were not significantly different. (iii) The pharmacokinetic parameters measured in pregnant patients during the third trimester of pregnancy were similar to those measured in healthy subjects. (iv) Residual concentrations of total and unbound CTX measured at 24 h were greater than the MICs for allegedly susceptible organisms, both on day 1 and at steady state. (v) During the final 3 months of pregnancy, the dosage schedule of CTX (2-g infusion per day) required no particular adjustment (i.e., neither a loading dose nor any increase in the maintenance dose).Ceftriaxone (CTX) is the first broad-spectrum cephalosporin prescribed on a single-daily-administration basis (24). This dosage schedule, which is unusual for a beta-lactam antibiotic, has been validated by a number of clinical studies since CTX came onto the market (11, 31). A pharmacodynamic and bacteriological approach taken together with the specific pharmacokinetics of the compound have formed the theoretical basis of a simplified administration schedule compared with those for other beta-lactams with shorter half-lives (9). The dosage recommended by the manufacturer (a single injection of 1 to 2 g every 24 h) is the consequence of an essential peculiarity of CTX: its prolonged terminal half-life (between 6.5 and 8.5 h) (21). The antibacterial spectrum of CTX is similar to that of other broad-spectrum cephalosporins. However, in comparison with other members of the group, it is less active against anaerobic organisms such as Bacteroides fr...

show abstract

Single-dose ceftriaxone kinetics in liver insufficiency

Cited by 38 publications

References 0 publications

Characteristics of ceftriaxone binding to immunoglobulin G and potential clinical significance

Characteristics of ceftriaxone binding to immunoglobulin G and potential clinical significance

Effect of cirrhosis on antibiotic efficacy in a rat model of pneumococcal pneumonia

Pharmacokinetics and protein binding of ceftriaxone during pregnancy

Contact Info

Product

Resources

About