Antibiotics protein binding

Singhvi, S.M., A.F. Heald, and E.C. Schreiber. 1978. Pharmacokinetics of cephalosporin antibiotics protein-binding considerations. Chemotherapy 24 121. 

Dmg distribution into tissue reservoirs depends on the physicochemical properties of the dmg. Tissue reservoirs include fat, bone, and the principal body organs. Access of dmgs to these reservoirs depends on partition coefficient, charge or degree of ionization at physiological pH, and extent of protein binding. Thus, lipophilic molecules accumulate in fat reservoirs and this accumulation can alter considerably both the duration and the concentration—response curves of dmg action. Some dmgs may accumulate selectively in defined tissues, for example, the tetracycline antibiotics in bone (see Antibiotics,tetracyclines). 

Enzymatic trapping Some -lactam antibiotics Penicillin-binding proteins... 

CF patients have larger volumes of distribution of many antibiotics due to an increased ratio of lean body mass to total body mass and lower fat stores. CF patients also have an enhanced total body clearance, although the exact mechanism has not been determined. Increased renal clearance, increased glomerular filtration rate, decreased protein binding, increased tubular secretion, decreased tubular reabsorption, extrarenal elimination, and increased metabolism have all been proposed as possible reasons for the increased clearance. 

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]. 

Beta-lactam antibiotics specifically bind with a number of proteins of cytoplasmic membranes known as penicillin-binding proteins (PBP). These proteins are enzymes involved in the reaction of transpeptidafion during the break up of cell membranes during growth and division. 

Pharmacology Macrolide antibiotics reversibly bind to the P site of the SOS ribosomal subunit of susceptible organisms and inhibit RNA-dependent protein synthesis. They may be bacteriostatic or bactericidal, depending on such factors as drug concentration. 

Methotrexate clearance can be decreased by the coadministration of NSAIDs however, this not usually a problem with the low doses of methotrexate used to treat arthritis. Methotrexate can be displaced from plasma protein binding sites by phenylbutazone, pheny-toin, sulfonylureas, and sulfonamides and certain other antibiotics. The antifolate effects of methotrexate are additive with those of other folate-inhibitory drugs, such as trimethoprim. 

Mechanism of Action An antibiotic that alters cell membrane permeability in susceptible microorganisms. Therapeutic Effect Bactericidal activity Pharmacokinetics Negligible absorption. Protein binding low. Excreted in urine. Poor removal in hemodialysis. Half-life 6 hr. 

A biochemical curiosity is the presence in egg white of the glycoprotein avidin.ab Each 68-kDa subunit of this tetrameric protein binds one molecule of biotin tenaciously with Kf 1015 M 1. Nature s purpose in placing this unusual protein in egg white is uncertain. Perhaps it is a storage form of biotin, but it is more likely an antibiotic that depletes the environment of biotin. A closely similar protein streptavidin is secreted into the culture medium by Streptomyces avidinii.c Its sequence is homologous to that of avidin. It has a similar binding constant for biotin and the two proteins have similar three-dimensional structures.3/d i Biotin binds at one end of a P barrel formed from antiparallel strands and is held by multiple hydrogen bonds and a conformational alteration that allows a peptide loop to close over the bound vitamin. 

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