20 research outputs found
Validation of a rapid and sensitive LC-MS/ MS method for determination of exemestane and its metabolites, 17β-hydroxyexemestane and 17β-hydroxyexemestane-17-O-β-D-glucuronide: Application to human pharmacokinetics study
10.1371/journal.pone.0118553PLoS ONE103e011855
Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients
10.1371/journal.pone.0054522PLoS ONE81
Su1310 Pregnancy and Birth Rates Are Decreased Among Women With IBD: Results of a Canadian Population-Based Cohort Study
A sensitive and specific liquid chromatography–tandem mass spectrometric method for determination of belinostat in plasma from liver cancer patients
Accuracy and Precision of Dilution Procedure for Exe.
<p>*Expressed as mean percentage (n = 4) of the mean value measured over the nominal value</p><p><sup>#</sup>Expressed as percentage of the standard deviation divided by the mean</p><p>Accuracy and Precision of Dilution Procedure for Exe.</p
Mean concentrations of a) Exe (b) 17DhExe and (c) Exe17Oglu in plasma samples of one representative breast cancer patient.
<p>Mean concentrations of a) Exe (b) 17DhExe and (c) Exe17Oglu in plasma samples of one representative breast cancer patient.</p
Product ion mass spectra of (a) Exe (b) 17DhExe and (c) Exe17Oglu.
<p>Product ion mass spectra of (a) Exe (b) 17DhExe and (c) Exe17Oglu.</p
Representative chromatograms of (a) Exe (b) 17DhExe and (c) Exe17Oglu at LLOQ and (a) Exe-d3, (b) DhExe-d3 as well as Exe17Oglu at 100 ng/mL as internal standards.
<p>Representative chromatograms of (a) Exe (b) 17DhExe and (c) Exe17Oglu at LLOQ and (a) Exe-d3, (b) DhExe-d3 as well as Exe17Oglu at 100 ng/mL as internal standards.</p
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Glucuronidation by UGT1A1 Is the Dominant Pathway of the Metabolic Disposition of Belinostat in Liver Cancer Patients
Belinostat is a hydroxamate class HDAC inhibitor that has demonstrated activity in peripheral T-cell lymphoma and is undergoing clinical trials for non-hematologic malignancies. We studied the pharmacokinetics of belinostat in hepatocellular carcinoma patients to determine the main pathway of metabolism of belinostat. The pharmacokinetics of belinostat in liver cancer patients were characterized by rapid plasma clearance of belinostat with extensive metabolism with more than 4-fold greater relative systemic exposure of major metabolite, belinostat glucuronide than that of belinostat. There was significant interindividual variability of belinostat glucuronidation. The major pathway of metabolism involves UGT1A1-mediated glucuronidation and a good correlation has been identified between belinostat glucuronide formation and glucuronidation of known UGT1A1 substrates. In addition, liver microsomes harboring UGT1A1*28 alleles have lower glucuronidation activity for belinostat compared to those with wildtype UGT1A1. The main metabolic pathway of belinostat is through glucuronidation mediated primarily by UGT1A1, a highly polymorphic enzyme. The clinical significance of this finding remains to be determined.ClinicalTrials.gov NCT00321594</p