Antibiotics serum protein binding

Antibiotic LogP > Serum protein binding (%) Serum concentration [jjg cm" ) during continuous infusion (500 mg h ) Peak serum levels after 500 mg kg 1... 

The P-lactam antibiotics continued to be the cynosure of synthesis. Some structure-activity relationships of peni-cillins O and cephalosporins 2 v/ere discussed. Timely reports aimed primarily toward the evaluation of the newer highly serum-bound penicillins dealt with the controversial relationship of drug-serum protein binding to clinical antimicrobial effectiveness. 3,14... 

The desired characteristics for an antibiotic are to have a wide antibacterial spectrum, to be an effective bactericide at low concentrations, high elution from the matrix for prolonged periods, thermal stabiHty, low allergy risks as well as low influence on the properties of the biomaterial and low serum protein binding [16,19]. Additionally, it is commonly used in the powder form. The antibiotics that implement most of these conditions are the aminoglycosides and glycopeptides. 

A number of workers have utilised electrophoresis to establish the formation of a complex between neomycin and the proteins in blood-serum and plasma- - -, 105,106,107,108,109,110,111. However, the nature of the complex is still unknown. Geitman has extensively studied the phenomena of protein-binding of antibiotics- -- -- - > 112. ... 

A study of the potency of the antibiotic daptomycin cited plasma protein binding of 92%, but it claimed only a 2-fold shift in potency in serum (expected 12-fold) [68]. This type of discrepancy is relatively common and can often reflect substantial binding to components in the "serum-free" media. In the cases of HIV-directed non-nucleotide reverse transcriptase inhibitors, this has been dealt with by measuring the unbound drug concentration in the "serum-free" medium and using that data to calculate the intrinsic, serum-free potency [69]. 

A consequence of the development of the large number of cephalosporins is that the molecular structures have become more and more complex. Alterations in the cephalosporin molecule have resulted in differences between cephalosporins in spectrum of activity, protein binding, peak serum level, serum half-life, route of excretion, cerebrospinal fluid levels and toxicity. Cephalosporins are semi-synthetic antibiotics derived from 7-aminocephalosporanic acid, which is also called the cephalosporin nucleus. The cephem ring ( nucleus") is composed of a (3-lactam ring fused with a dihydrothiazine ring (Figure 1). 

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