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.
Van den Berg
C L
CL
Cancer Therapy and Research Center, San Antonio, TX 78229.
McGill
J R
JR
Kuhn
J G
JG
Walsh
J T
JT
De La Cruz
P S
PS
Davidson
K K
KK
Wahl
G M
GM
Von Hoff
D D
DD
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