Scaling Laws for Plasma Concentrations and Tolerable Doses of Anticancer Drugs -- Cancer Research

Abstract:
General scaling laws are developed for projecting measurements of the plasma concentrations of anticancer drugs from laboratory animals to humans and among humans of different sizes. Associated scaling laws for critical drug doses are established from these laws. Broad categories of single and periodic i.v. bolus dosings are considered. Validity of the relations is shown using measurement from the literature for several well-known cytotoxic agents. The scaling theory is also shown to apply to novel anticancer drugs now available or presently under development, as represented by the p.o. administered prodrug capecitabine, the gene silencing inhibitor zebularine, and the blood vessel inhibitor bevacizumab(Avastin). Scaling considerations for the modern practice of combination chemotherapy are also discussed.