CHROMATOGRAPHY AS AN ANALYTICAL TOOL FOR SELECTED ANTIBIOTIC CLASSES - A REAPPRAISAL ADDRESSED TO PHARMACOKINETIC APPLICATIONS

The first antibiotic discovered, penicillin, appeared on the market ju st after the Second World War. Intensive research in subsequent years led to the discovery and development of cephalosporins, aminoglycoside s, tetracyclines and rifamycin. The chemotherapeutic quinolones and th e more recently discovered fluoroquinolones have added promising new t herapeutic weapons to fight the microbial challenge. The major role ph armacokinetics has played in developing these compounds should be high lighted. Plasma concentration-time profiles and the therapeutic activi ty evoked by these compounds allow the therapeutic window, doses and d ose turnovers to be appropriately defined, as well as possible dose ad justment to be made in renal failure. The pharmacokinetics of antimicr obial 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 s atisfactorily solved the problem of antimicrobial agent assay for phar macokinetic, bioavailability and bioequivalence purposes alike. Indeed , in these studies, plasma concentrations of the given analyte must be followed up for a period greater than or equal to 3 times the half-li fe, which calls for specific sensitive assays. In this review, the aut hors have described the analytical methods employed in the pharmacokin etics of antibiotics, including some chemotherapeutic agents which are used in medical practice as alternatives to antibiotics. The pharmaco kinetic characteristics of each class of drugs are also briefly descri bed, and some historical and chemical notes on the various classes are given. (C) 1998 Elsevier Science B.V. All rights reserved.