Pharmacokinetics of hydroxyurea in nude mice.
Extrachromosomal DNA is the predominant form of gene amplification in human tumors. Hydroxyurea (HU) concentrations of 100-150 microM 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 t1/2 determination, mice were injected with HU 100 mg/kg. A plasma concentration of 159 microM was achieved and a t1/2 of 11.3 min determined. Based on these findings, In vivo elimination studies will require frequent administration of HU to maintain plasma concentrations from 100 to 150 microM.
Cancer Therapy and Research Center, San Antonio, TX 78229.
C L
CL
Van den Berg
J R
JR
McGill
J G
JG
Kuhn
J T
JT
Walsh
P S
PS
De La Cruz
K K
KK
Davidson
G M
GM
Wahl
D D
DD
Von Hoff
D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects*; D006207:Half-Life; D006918:Hydroxyurea / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014018:Tissue Distribution
D003470:Culture Media; D004273:DNA, Neoplasm; D006918:Hydroxyurea