Stereoselective Separations of Chiral Anticancer Drugs and Their Application to Pharmacodynamic and Pharmacokinetic Studies

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In the past few years, it has become clear that individual stereo-isomers— especially the enantiomers— of a biologically active chiral molecule may differ in potency, pharmacological action, metabolism, toxicity, plasma disposition, and urine excretion kinetics. This situation exists in all classes of therapeutically active agents including chiral anticancer agents. The chiral compounds used in standard and experimental cancer chemotherapy include leucovorin (LV), ifosfamide (IFF), buthionine sulfoximine (BSO), and verapamil (VER), Analytical methods for stereoselective separation of each of these compounds have been developed and applied to pharmacokinetic and pharmacodynamic studies. Pharmacological differences have been found between stereoisomers of all of these compounds and it is evident that the clinical effectiveness of these agents would be enhanced by the administration of only a single isomer.

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