Antimicrobial pharmacokinetic properties

This wide range of pharmacokinetic properties, along with thek ease of administration, broad spectmm antimicrobial activity, and noninterference with host-defense mechanisms is responsible for thek widespread use five decades after thek discovery. 

Brogden RN, Peters DH Teicoplanin A reappraisal of its antimicrobial activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1994 47 823-854. 

Although all tetracyclines have a similar mechanism of action, they have different chemical structures and are produced by different species of Streptomyces. In addition, structural analogues of these compounds have been synthesized to improve pharmacokinetic properties and antimicrobial activity. While several biological processes in the bacterial cells are modified by the tetracyclines, their primary mode of action is inhibition of protein synthesis. Tetracyclines bind to the SOS ribosome and thereby prevent the binding of aminoacyl transfer RNA (tRNA) to the A site (acceptor site) on the 50S ri-bosomal unit. The tetracyclines affect both eukaryotic and prokaryotic cells but are selectively toxic for bacteria, because they readily penetrate microbial membranes and accumulate in the cytoplasm through an energy-dependent tetracycline transport system that is absent from mammalian cells. 

Many antimicrobial agents have similar pharmacokinetic properties when given orally or parenterally (ie, tetracyclines, trimethoprim-sulfamethoxazole, quinolones, chloramphenicol, metronidazole, clindamycin, rifampin, linezolid and fluconazole). In most cases, oral therapy with these drugs is equally effective, is less costly, and results in fewer complications than parenteral therapy. 

Parenteral preparations with antimicrobial activity, which depends on the causative pathogenic microorganism, and pharmacokinetic properties that meet most of these criteria include procaine penicillin G (aqueous suspension), amoxicillin trihydrate-clavulanate potassium combination (aqueous suspension), and enro-floxacin (solution). Enrofloxacin is not approved for use... 

In the preparation of semisynthetic cephalosporins, the following improvements are sought (a) increased acid stability, (b) improved pharmacokinetic properties, particularly better oral ab.sorption, ic) broadened antimicrobial spectrum. (d) increased activity agaiast resistant microorganisms (as a result of resistance to enzymatic destruction, improved penetration. increased receptor affinity, etc.), (e) decreased allergenicity, and (f) increased tolerance after parenteral administration. 

Integration of both pharmacokinetic and pharmacodynamic properties of an agent is important when choosing antimicrobial therapy to ensure efficacy and to prevent resistance. Early researchers relied solely on pharmacokinetic properties such as area under the drug concentration curve (AUC), maximum observed concentration (peak), and drug half-life to optimize therapy. Pharmacodynamics is the study of the relationship between drug concentration and the effects on the microorganism (see Chap. 103). Researchers now realize the... 

Perry CM, Whittington R, McTavish D. Fluconazole An update of its antimicrobial activity, pharmacokinetic properties, and ther eutic use in vaginal candidiasis. Drugs 1995 49 984-1006. 

The antimicrobial activity, pharmacokinetic properties, and toxicity profile of tobramycin (nebcin) are very similar to those of gentamicin. Dosages and serum concentrations are identical with those for gentamicin. Tobramycin (tobrex) also is available in ophthalmic ointments and solutions. 

The structural features of the quinolones strongly Influence the antimicrobial and pharmacokinetic properties of this class of drugs. The essential pharmacophore for activity is the carboxy-4-pyridone nucleus (Fig. 

Currently, vancomycin is the only approved glycopeptide available for use in the United States. For several decades, vancomycin has been considered the most potent antimicrobial against Gram-positive pathogens. The pharmacokinetic properties of vancomycin are listed below. 

TABLE 2.2 Influence of Lipid Solubility of Antimicrobial Drugs on Pharmacokinetic Properties (ADME) ... 

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