STEREOSELECTIVE SEPARATIONS OF CHIRAL ANTICANCER DRUGS AND THEIR APPLICATION TO PHARMACODYNAMIC AND PHARMACOKINETIC STUDIES

In the past few years, it has become clear that individual stereo-isom ers-especially the enantiomers-of a biologically active chiral molecul e may differ in potency, pharmacological action, metabolism, toxicity, plasma disposition, and urine excretion kinetics. This situation exis ts in all classes of therapeutically active agents including chiral an ticancer agents. The chiral compounds used in standard and experimenta l cancer chemotherapy include leucovorin (LV), ifosfamide (IFF), buthi onine sulfoximine (BSO), and verapamil (VER). Analytical methods for s tereoselective separation of each of these compounds have been develop ed and applied to pharmacokinetic and pharmacodynamic studies. Pharmac ological differences have been found between stereoisomers of all of t hese compounds and it is evident that the clinical effectiveness of th ese agents would be enhanced by the administration of only a single is omer.