Simultaneous determination of taxol and its metabolites in microsomal samples by a simple thin-layer chromatography radioactivity assay--inhibitory effect of NK-104, a new inhibitor of HMG-CoA reductase.
The inhibitory effect of NK-104, a potent inhibitor of HMG-CoA reductase, on taxol metabolism was examined using radio-TLC. This method is described for in vitro measurement of taxol metabolites as an alternative to the commonly used HPLC assay. After incubation of 14C-taxol with human liver microsomes, the supernatants were developed using a solvent system consisting of toluene-acetone-formic acid (60:39:1, v/v) and quantified with a bioimaging analyzer. The described method provides a valuable tool for the simultaneous determination of unchanged taxol and its major metabolites. There was no inhibitory effect of NK-104 on CYP-mediated metabolism of taxol in human liver microsomes.
Fujino
H
H
Tokyo Research Laboratories, Kowa Company Ltd., Higashimurayama, Japan.
Yamada
I
I
Shimada
S
S
Yoneda
M
M
D000972:Antineoplastic Agents, Phytogenic / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000493:pharmacokinetics*; D002855:Chromatography, Thin Layer / Q000379:methods*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000378:metabolism; D017239:Paclitaxel / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000493:pharmacokinetics*; D011804:Quinolines / Q000494:pharmacology*; D011874:Radiometry / Q000379:methods*; D015203:Reproducibility of Results
D000972:Antineoplastic Agents, Phytogenic; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; C108475:pitavastatin; D017239:Paclitaxel