Antimicrobial protein binding

In subsequent studies attempting to find a correlation of physicochemical properties and antimicrobial activity, other parameters have been employed, such as Hammett O values, electronic distribution calculated by molecular orbital methods, spectral characteristics, and hydrophobicity constants. No new insight on the role of physiochemical properties of the sulfonamides has resulted. Acid dissociation appears to play a predominant role, since it affects aqueous solubiUty, partition coefficient and transport across membranes, protein binding, tubular secretion, and reabsorption in the kidneys. An exhaustive discussion of these studies has been provided (10). 

IV IV infusion over 20 minutes results in peak plasma levels of imipenem antimicrobial activity that range from 14 to 83 mcg/mL, depending on the dose. Plasma levels declined to 1 mcg/mL or less in 4 to 6 hours. Peak plasma levels of cilastatin following a 20-minute IV infusion range from 15 to 88 mcg/mL, depending on the dose. The plasma half-life of each component is approximately 1 hour. Protein binding is 20% for imipenem and 40% for cilastatin. 

Nitrofurantoin is administered orally and is rapidly and almost completely absorbed from the small intestine only low levels of activity are achieved in serum because the drug is rapidly metabolized. Relatively high protein binding (about 70%) also affects serum levels, reducing potential for systemic toxicity and alteration of intestinal flora. Relative tissue penetration is much lower than other antimicrobials for UTIs, and therefore, nitrofurantoin is not indicated in the therapy of infections such as pyelonephritis and renal cortical or perinephric abscesses. Nitrofurantoin is rapidly excreted by glomerular filtration and tubular secretion to yield effective urinary levels. In moderate to severe renal dysfunction, toxic blood levels may occur while urinary levels may be inadequate. The drug is inactivated in the liver. 

Chapter 1 discussed the principles of drug pharmacokinetics here the importance of volumes of distribution (Pj), drug ionization and protein binding are outlined for antimicrobial drugs. 

Antimicrobial agent Volume of distribution (l/kg) Half-life (h) Acid-base status Protein binding (%) Elimination Indications Dose... 

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... 

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