Binding of Antibiotics to the Human Intracellular Erythrocyte Proteins Hemoglobin and Carbonic Anhydrase

Kornguth, Margaret L.; Kunin, Calvin M.

doi:10.1093/infdis/133.2.185

Cited by 38 publications

(16 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The binding of drugs to serum proteins is believed to be due mainly to an interaction between the drug and serum albumin. However, other serum proteins, including enzymes, have been shown to interact with some drugs, e.g., tetracycline (Kornguth and Kunin, 1976). Transferrin and IgM have not previously been shown to interact with any of the drugs which we found to neutralise the inhibitory factor.…”

Section: Discussioncontrasting

confidence: 47%

The inhibitory effect of serum on the growth of Torulopsis glabrata

Petrou

Rogers²

1988

Journal of Medical Microbiology

View full text Add to dashboard Cite

Summary.Normal human plasma and serum were found to inhibit the growth of Torulopsis glabrata and, to a lesser extent, other yeasts. The factor responsible for the inhibition of T. glabrata was not dialysable, was heat stable at 56" C for up to 4 h and could be partly removed by absorption with viable T. glabrata but not Candida albicans. It was fungistatic at low concentrations and fungicidal at high concentrations, stable up to 4 years between -20" C and -70" C, but for only a few weeks at 4" C. Studies with Cohn fractions of serum showed that the inhibitory components were in either the alpha or beta globulin fraction or both. The combined effects of transferrin and IgM accounted for about 70% of the total inhibition observed. We were unable to identify the component responsible for the residual inhibition of growth. The inhibitory effect was totally neutralised by tetracyclines, quinolones, sulphamethoxazole and by very low concentrations of polyenes, imidazoles and 5-fluorocytosine.

show abstract

Section: Discussioncontrasting

confidence: 47%

The inhibitory effect of serum on the growth of Torulopsis glabrata

Petrou

Rogers²

1988

Journal of Medical Microbiology

View full text Add to dashboard Cite

show abstract

“…For example, clindamycin which binds to alpha-1-acid glycoprotein, displays 40% protein binding in MHB containing 40 g/liter of human albumin but displays 85% binding in human serum (29). Moreover, whole blood cells, fractions of blood cells, and hemoglobin itself bind and possibly inactivate antibiotics in vivo or in vitro when these are used to supplement bacterial growth media (5,52,98).…”

Section: Problems and Challenges Of Current Modelsmentioning

confidence: 99%

Protein Binding: Do We Ever Learn?

Zeitlinger

Derendorf

Mouton

et al. 2011

Antimicrob Agents Chemother

226

194

View full text Add to dashboard Cite

6Although the influence of protein binding (PB) on antibacterial activity has been reported for many antibiotics and over many years, there is currently no standardization for pharmacodynamic models that account for the impact of protein binding of antimicrobial agents in vitro. This might explain the somewhat contradictory results obtained from different studies. Simple in vitro models which compare the MIC obtained in protein-free standard medium versus a protein-rich medium are prone to methodological pitfalls and may lead to flawed conclusions. Within in vitro test systems, a range of test conditions, including source of protein, concentration of the tested antibiotic, temperature, pH, electrolytes, and supplements may influence the impact of protein binding. As new antibiotics with a high degree of protein binding are in clinical development, attention and action directed toward the optimization and standardization of testing the impact of protein binding on the activity of antibiotics in vitro become even more urgent. In addition, the quantitative relationship between the effects of protein binding in vitro and in vivo needs to be established, since the physiological conditions differ. General recommendations for testing the impact of protein binding in vitro are suggested.Binding to plasma proteins plays a major role in drug therapy as this binding provides a depot for many compounds, affects pharmacokinetics (PK) and pharmacodynamics (PD) of drugs, and may influence the metabolic modification of ligands (34,104). Protein binding (PB) of antibiotics may affect the efficacy of antimicrobial therapy in two ways. First, only the non-protein-bound fraction of a drug in plasma can penetrate into and equilibrate with the extravascular space (13). Penetration into the extravascular space is highly important for antimicrobial therapy, as the majority of bacterial and fungal infections occur in the interstitial fluid of tissues or in other body fluids than blood (113). PB also affects drug clearance from the body. For antibiotics eliminated by tubular secretion or hepatic metabolism, high PB is associated with lowered drug elimination. Additionally, PB negatively correlates with glomerular filtration, since only the free drug is filtered (63). On the other hand, small fluctuations in protein binding usually have no effect on average unbound concentrations, and this is especially the case for drugs with a low extraction ratio (11). Changes in protein binding can also alter the volume of distribution and, hence, the half-life, which may, in turn, modify the time above MIC. Extensive reviews on the impact of PB on pharmacokinetics of drugs are available (12,13,27,29,82,86).The second effect of PB is demonstrated by the impact on the antibacterial activity. Over many decades, various methods were used to show that only the non-protein-bound fraction of an antibiotic is microbiologically active (10,28,70,111). For important antibiotic classes, such as penicillins and quinolones, clear relationships between the percenta...

show abstract

“…al. [20]. In that study experiments with pure preparations of carbonic anhydrase revealed that the CA isozyme is the major binder of the tetracyclines and that zinc is required for binding did not inhibit enzymatic activity of carbonic anhydrase.…”

Section: The Structural Formulae Of Effective Antibioticsmentioning

confidence: 91%

“…Tumor associated carbonic anhydrase isozymes were further purified by Sepharose 4B-L-tyrosine-sulfonamide affinity gel [20] had the concentrations 4 £ 10…”

Section: Methodsmentioning

confidence: 99%