ABSTRACT
This ABIGENE pharmacokinetic (PK) study sought mainly to characterize the unchanged drug PK during long-term abiraterone acetate (AA) administration in advanced prostate cancer patients (81 patients). It was observed that individual AA concentrations remained constant over treatment time, with no noticeable changes during repeated long-term drug administration for up to 120 days. There was no correlation between AA concentrations and survival outcomes. However, a significant association between higher AA concentrations and better clinical benefit was observed (p = 0.041). The safety data did not correlate with the AA PK data. A significant positive correlation (r = 0.40, p < 0.001) was observed between mean AA concentration and patient age: the older the patient, the higher the AA concentration. Patient age was found to impact steady-state AA concentration: the older the patient, the higher the mean AA concentration. Altogether, these data may help to guide future research and clinical trials in order to maximize the benefits of AA metastatic castration-resistant prostate cancer patients.
Subject(s)
Abiraterone Acetate , Prostatic Neoplasms, Castration-Resistant , Humans , Male , Abiraterone Acetate/pharmacokinetics , Abiraterone Acetate/therapeutic use , Abiraterone Acetate/administration & dosage , Prostatic Neoplasms, Castration-Resistant/drug therapy , Prostatic Neoplasms, Castration-Resistant/pathology , Aged , Middle Aged , Aged, 80 and over , Follow-Up Studies , Neoplasm Metastasis , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/administration & dosageABSTRACT
During investigations on the peroxidase-catalysed oxidation of polyhydroxylated monoaromatic substrates such as 5-methylpyrogallol, we observed a spectacular dimerisation proceeding by dearomatisation in contrast with most common reaction patterns involving phenolics oxidation and dimerization. A tetracyclic fused product featuring an unusual 2-oxatetracyclo [6.3.1.01,6.04,12] dodecan-3-one core was obtained and characterized by combined NMR techniques and high resolution mass spectroscopy (HRMS). This is an example of a spontaneous cascade triggered by a simple enzymatic reaction that could provide new options for biosynthetic hypothesis and a synthetic method to access this complex core in one operation.
