Chromatography as an analytical tool for selected antibiotic classes: a reappraisal addressed to pharmacokinetic applications.
The first antibiotic discovered, penicillin, appeared on the market just after the Second World War. Intensive research in subsequent years led to the discovery and development of cephalosporins, aminoglycosides, tetracyclines and rifamycin. The chemotherapeutic quinolones and the more recently discovered fluoroquinolones have added promising new therapeutic weapons to fight the microbial challenge. The major role pharmacokinetics has played in developing these compounds should be highlighted. Plasma concentration-time profiles and the therapeutic activity evoked by these compounds allow the therapeutic window, doses and dose turnovers to be appropriately defined as well as possible dose adjustment to be made in renal failure. The pharmacokinetics of antimicrobial agents were initially explored by using microbiological methods, but these lack specificity. The HPLC technique with UV, fluorometric, electrochemical and, in some cases, mass spectrometry detection has satisfactory solved the problem of antimicrobial agent assay for pharmacokinetic, bioavailability and bioequivalence purposes alike. Indeed, in these studies, plasma concentrations of the given analyte must be followed up for a period > or = 3 times the half-life, which calls for specific sensitive assays. In the review, the authors have described the analytical methods employed in the pharmacokinetics of antibiotics, including some chemotherapeutic agents which are used in medical practice as alternatives to antibiotics. The pharmacokinetic characteristics of each class of drugs are also briefly described, and some historical and chemical notes on the various classes are given.
I.P.A.S. S.A., Clinical Pharmacology Department, Ligornetto, Switzerland.
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D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000493:pharmacokinetics*; D002845:Chromatography; D006801:Humans
D000900:Anti-Bacterial Agents