Pharmacokinetics, tissue distribution, and metabolism of novel DNA topoisomerase I inhibitor yuanhuacine in rabbit.
A liquid chromatography/tandem mass spectrometry method was developed and validated for the quantitative determination of yuanhuacine (YHC), a daphne diterpene ortho-ester anticancer agent, and identification of its metabolites. Pharmacokinetic behaviour, tissue distribution, and metabolism were investigated in rabbit. YHC plasma data best fitted to a two-compartment model and were characterized by an elimination half-life t(1/2)(beta) of 11.1 h following intravenous administration. Tissue distribution studies did not identify any tissues having a high affinity for YHC. The main metabolites are proposed to be M392I, M392II, and M390, resulting from the ortho-ester group and aromatic ester bond being cleaved off simultaneously during Phase I metabolism. This investigation contributes to an understanding of the metabolism of daphne diterpene ortho-esters.
Zhang
S X
SX
State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian, P. R. China. zhangsx56@yahoo.com.cn
Yang
P W
PW
Zhang
D C
DC
Dong
W Q
WQ
Zhang
F H
FH
Sun
Y M
YM
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D004224:Diterpenes / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics*; D006207:Half-Life; D008954:Models, Biological; D011817:Rabbits; D053719:Tandem Mass Spectrometry / Q000379:methods; D014018:Tissue Distribution; D059004:Topoisomerase I Inhibitors
D004224:Diterpenes; D059004:Topoisomerase I Inhibitors; C029912:Yuanhuacin