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Metabolic difference of CZ48 in human and mouse liver microsomes.

Abstract：

:CZ48, chemically camptothecin-20-O-propionate hydrate, is currently under clinical investigation. The kinetics of the metabolite camptothecin (CPT) formation and of CZ48 depletion in mouse and human liver microsomes in the presence or absence of NADPH was examined. The formation rate of camptothecin in human liver microsomes was significantly higher than that in mouse with mean K(m)s of 1.9 and 0.5 nM and V(max)s of 9.3 and 2.2 pmol/min/mg, respectively. However, the apparent intrinsic clearance (V(max)/K(m)) ratios for camptothecin in human and mouse liver microsomes were not significantly different from each other (4.9 versus 4.4) in the presence of NADPH. The depletion of CZ48 in human microsomes was four times faster with 4.55% of CZ48 remaining intact while in mouse 19.11% of the drug remained unchanged after 60 min. These results suggest that there is a remarkable species difference of CZ48 biotransformation between human and mouse. The depletion rate of CZ48 in human liver microsomes is considerably higher than that in the mouse.

journal_name

Int J Mol Sci

journal_title

International journal of molecular sciences

authors

Liu X,Dejesus A,Cao Z,Vardeman D,Giovanella B

doi

10.3390/ijms13055498

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

5498-505

issue

5

issn

1422-0067

pii

ijms-13-05498

journal_volume

13

pub_type

杂志文章

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