Pharmacokinetics of hydroxyurea in nude mice

Abstract

Extrachromosomal DNA is the predominant form of gene amplification In human tumors. Hydroxyurea (HU) concentrations of 100-150 IAM have been promising In vitro for extrachromosomal DNA elimination. The study objective was to determine the HU dose-concentration relationship in nude mice with HU doses from 0 to 200 mg/kg. For HU t_1/2 determination, mice were Injected with HU 100 mg/kg. A plasma concentration of 159 p.M was achieved and a t_1/2 of 11.3 mln determined. Based on these findings, In vivo elimination studies will require frequent administration of HU to maintain plasma concentrations from 100 to 150 µM.