Pharmacokinetics of chemotherapy.

John W. Cullen, MD, is a Pediatric Oncologist at Children’s Hospital in Denver, Colorado. The optimal utilization of a chemotherapeutic agent depends on an understanding of the factors involved in absorption, distribution, biotransformation, cellular uptake, method of action and routes of excretion. This presentation gave a brief introduction to these concepts. The treatment of childhood cancer usually involves the use of multiple drugs. The use of drugs from different classes with different methods of action theoretically would give a higher chance of cell kill. The classes of drugs most frequently used in childhood cancer therapy are antimetabolites, alkylating agents, antibiotics, antistathmokinetic agents and some miscellaneous drugs. Antimetabolites may interfere with DNA, RNA or protein synthesis. Thioguanine and 6-mercaptopurine are examples of antimetabolites which interfere with proper production of DNA. Alkylating agents such as nitrogen mustard and cyclophosphamide bind from one chain of DNA to another. This process known as intercalation interferes with separation of the chains, subsequent replication and division. Daunomycin, an antibiotic, also intercalates within the DNA strands while Bleomycin causes scission of the strands. Vincristine is an antistathmokinetic agent. It destroys the ability of the chromosomes to retract from the center of a cell