Pharmacokinetics and Metabolism of Acridine Drugs

Pharmacokinetic reasons have strong influence on applications of acridine drugs. Balancing of processes such as absorption, distribution, metabolism and excretion (ADME) is necessary for their proper action. For treatment of CNS tumor or neurodegenerative diseases, the ability of acridines to penetrate blood–brain barrier is important. Pharmacokinetic profiles of acridine drugs can be improved by conjugation with various nanoobjects such as liposomes or dendrimers. Despite pharmacokinetic limitation for transport of intercalators, the design of acridines with efficient diffusion to tumor tissue is possible. During the metabolism, usually, acridines are converted to more hydrophilic species by oxidation. However, a formation of practically insoluble acridones can also appear. In tumor cells, the reductive environment can provide partially hydrogenated acridines. Rapid metabolism of some acridines can lead to failure of the drugs in clinical trials.