Cellular, pharmacokinetic, and pharmacodynamic aspects of response to camptothecins: can we improve it?
The camptothecins provide a novel class of effective anticancer agents that exert their action against DNA topoisomerase I. Members of the camptothecins include topotecan, irinotecan, 9-aminocamptothecin, and 9-nitrocamptothecin, which are analogs of the plant alkaloid 20(S)-camptothecin. These agents vary in their antitumor efficacy and toxicity. Several pharmacokinetic and pharmacodynamic factors including cellular efflux, modulation of topoisomerases I and II, lactone stability, alterations in metabolism, and drug-drug interactions, influence the antitumor response and toxicity of these agents. Preclinical studies suggest that protracted schedules of administration produce greater antitumor effect than bolus administration. However, the optimal treatment regimens and administration schedules of these agents have yet to be established in clinical studies.
Jung
L L
LL
University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
Zamboni
W C
WC
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D002986:Clinical Trials as Topic / Q000379:methods; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors
D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; D004250:DNA Topoisomerases, Type II; D002166:Camptothecin