Next Article in Journal
Evaluation of Antioxidant and Antiproliferative Properties of Three Actinidia (Actinidia kolomikta, Actinidia arguta, Actinidia chinensis) Extracts in Vitro
Previous Article in Journal
A Glutamic Acid-Producing Lactic Acid Bacteria Isolated from Malaysian Fermented Foods
Article Menu

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2012, 13(5), 5498-5505; doi:10.3390/ijms13055498

Metabolic Difference of CZ48 in Human and Mouse Liver Microsomes

CHRISTUS Stehlin Foundation for Cancer Research, 10301 Stella Link, Houston, TX 77025, USA
Author to whom correspondence should be addressed.
Received: 27 March 2012 / Revised: 27 April 2012 / Accepted: 28 April 2012 / Published: 8 May 2012
View Full-Text   |   Download PDF [249 KB, uploaded 19 June 2014]   |  


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 Kms of 1.9 and 0.5 nM and Vmaxs of 9.3 and 2.2 pmol/min/mg, respectively. However, the apparent intrinsic clearance (Vmax/Km) 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. View Full-Text
Keywords: metabolism; biotransformation; cytochromeP450; UDP-glucuronosyltransferases; microsomes; CZ48; camptothecin metabolism; biotransformation; cytochromeP450; UDP-glucuronosyltransferases; microsomes; CZ48; camptothecin

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Liu, X.; DeJesus, A.; Cao, Z.; Vardeman, D.; Giovanella, B. Metabolic Difference of CZ48 in Human and Mouse Liver Microsomes. Int. J. Mol. Sci. 2012, 13, 5498-5505.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top