Characteristics of ceftriaxone binding to immunoglobulin G and potential clinical significance

Abstract

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

Pharmacokinetic/Pharmacodynamic Target Attainment Based on Measured versus Predicted Unbound Ceftriaxone Concentrations in Critically Ill Patients with Pneumonia: An Observational Cohort Study

“…Second, there might be covariates potentially influencing protein binding that were not measured or included in this study. Immunoglobulin G (IgG) has been reported to affect unbound ceftriaxone plasma concentrations when reaching very high concentrations, or in patients with severe hypoalbuminemia [ 27 , 28 ]. In the present study, most patients had moderate hypoalbuminemia, and none of the patients received IgG treatment during ceftriaxone treatment.…”

Influence of Human Serum on Pharmacodynamic Properties of an Investigational Glycopeptide, LY333328, and Comparator Agents against Staphylococcus aureus

“…It is thus possible that there are other minor proteins in serum that bind the cephalosporins cefazolin and ceftriaxone, although the identity of these proteins is uncertain. Sun et al showed that ceftriaxone is capable of binding to immunoglobulin G in serum and that this binding could be particularly important at low total drug concentrations, such as those used in our experiments (17). The possibility also exists that factors present in MHB are occupying sites on the albumin in MHBA that the two cephalosporins would normally bind to, although it is highly unlikely that such factors would be present in sufficient amounts to have an appreciable effect.…”

Adjuvant intraperitoneal ceftriaxone in the treatment of septic peritonitis in horses

“…The free form represents the active portion of the drug. 13 Thus, high systemic doses are required to achieve the desired therapeutic effect. However, if used intraperitoneally, it is available for a longer time 14 and may lead to the amplification of the therapeutic effect and also may provide better clinical results.…”