CLINICAL PHARMACOKINETICS OF CAMPTOTHECIN TOPOISOMERASE-I INHIBITORS

In this review the clinical pharmacokinetics of campthothecin topoisom erasae I inhibitors, an important new class of anti-cancer drugs, is d iscussed. Two prototypes, topotecan and irinotecan, are currently mark eted in many European countries and the USA for the treatment of patie nts with ovarian and colorectal cancer, respectively. Other camptothec in derivatives, including lurtotecan, 9-aminocamptothecin (9-AC) and 9 -nitrocamptothecin (9-NC), are at different stages of clinical develop ment. The common property of camptothecin analogues is their action ag ainst DNA topoisomerase I, but beyond this similarity the compounds di ffer widely in terms of antitumour efficacy, pharmacology, pharmacokin etics and metabolism. We review chemistry, mechanism of action, stabil ity and bioanalysis of the camptothecins. Dosage and administration, s tatus of clinical application, pharmacokinetics, pharmacodynamics and drug interactions are discussed.