Abstract
Total (added) drug concentrations other than unbound concentrations have been used to estimate the in-vitro enzyme kinetic parameters for 5,6-dimethylxanthenone-4-acetic acid (DMXAA), an experimental anti-cancer drug. This study aimed to investigate the non-specific binding of DMXAA to liver microsomes from variousspecies and to microsomesfrom human lymphoblastoid cells expressing drug-metabolising enzymes, and to examine the effect of the binding on the estimation of enzyme kinetic parameters for DMXAA in-vitro. The separation of unbound DMXAA was conducted by ultrafiltration and DMXAA concentrations were determined by validated HPLC. The results indicated that DMXAA was bound to liver microsomes and lymphoblastoid cell microsomes to a small extent (free fraction in microsomes, f(u(mic)) mostly > 0.85). Correction forthe unbound DMXAA concentration resulted in slightly lower apparent Michaelis-Menten constant (Km) values, but with the maximal velocity of reaction (Vmax) unchanged, leading to slightly higher unbound Vmax/Km values. These results indicate that the non-specific binding of DMXAA to microsomes is insignificant and has little impact on the enzyme kinetic estimation in-vitro.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
